Journal ArticleCells · December 3, 2024
Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation o ...
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Journal ArticleJ Leukoc Biol · November 4, 2024
In immuno-oncology, the focus has traditionally been on αβ T cells, and immune checkpoint inhibitors that primarily target PD-1 or CTLA4 in these lymphocytes have revolutionized the management of multiple human malignancies. However, recent research highli ...
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Other · September 16, 2024
<div>Abstract<p>Purpose: Immune checkpoint blockade holds promise for treating BCG-unresponsive non-muscle invasive bladder cancer. In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal a ...
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Other · September 16, 2024
<div>Abstract<p>Purpose: Immune checkpoint blockade holds promise for treating BCG-unresponsive non-muscle invasive bladder cancer. In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal a ...
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Journal ArticleCells · June 28, 2024
Understanding tumor-host immune interactions and the mechanisms of lung cancer response to immunotherapy is crucial. Current preclinical models used to study this often fall short of capturing the complexities of human lung cancer and lead to inconclusive ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · June 3, 2024
BACKGROUND: Cigarette smoke exposure has been linked to systemic immune dysfunction, including for B-cell and immunoglobulin (Ig) production, and poor outcomes in patients with ovarian cancer. No study has evaluated the impact of smoke exposure across the ...
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Other · June 3, 2024
<p>Supplemental Table 9: Hazard ratios and 95% confidence intervals between smoking and ovarian cancer risk by tumor immune infiltration of B cells among Type II tumors, NHS and NHSII</p> ...
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Other · June 3, 2024
<div>AbstractBackground:<p>Cigarette smoke exposure has been linked to systemic immune dysfunction, including for B-cell and immunoglobulin (Ig) production, and poor outcomes in patients with ovarian cancer. No study has evaluated the i ...
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Other · June 3, 2024
<p>Supplemental Table 7: Hazard ratios and 95% confidence intervals between smoking and ovarian cancer risk by tumor immune infiltration of B cells, NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Table 6: Odds ratios and 95% confidence intervals for positivity of tumor immune infiltration of various types of B cells and immunoglobulins by adult smoking status among cases only within two years before diagnosis, NHS and ...
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Other · June 3, 2024
<p>Supplemental Figure 1: Flow chart for the selection of ovarian cancer cases in the Nurses’ Health Study (NHS) and NHSII, limited to ovarian cancer diagnosis, available tissue, available data on parental smoke exposure, and successful multi ...
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Other · June 3, 2024
<p>Supplemental Table 8: Hazard ratios and 95% confidence intervals between smoking and ovarian cancer risk by tumor immune infiltration of immunoglobulins, NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Table 3: Characteristics of women with ovarian cancer in NHS and NHSII, overall and who had tumor tissue on the TMAs and information about lifetime cigarette smoke exposure</p> ...
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Other · June 3, 2024
<p>Supplemental Table 4: Percent positive immune cells or Ig positive cells in the tumor among all cells in the tumor by ovarian tumor subtype in NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Table 6: Odds ratios and 95% confidence intervals for positivity of tumor immune infiltration of various types of B cells and immunoglobulins by adult smoking status among cases only within two years before diagnosis, NHS and ...
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Other · June 3, 2024
<p>Supplemental Table 9: Hazard ratios and 95% confidence intervals between smoking and ovarian cancer risk by tumor immune infiltration of B cells among Type II tumors, NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Table 2: Age-standardized baseline characteristics by parental smoking during childhood or adolescence, NHS (1982) and NHSII (1999)</p> ...
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Other · June 3, 2024
<p>Supplemental Table 10: Hazard ratios and 95% confidence intervals between smoking and ovarian cancer risk by tumor immune infiltration of immunoglobulins among Type II tumors, NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Table 8: Hazard ratios and 95% confidence intervals between smoking and ovarian cancer risk by tumor immune infiltration of immunoglobulins, NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Table 5: Odds ratios and 95% confidence intervals for positivity of tumor immune infiltration of various types of B cells and immunoglobulins by smoking status among cases in NHS only</p> ...
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Other · June 3, 2024
<p>Supplemental Table 4: Percent positive immune cells or Ig positive cells in the tumor among all cells in the tumor by ovarian tumor subtype in NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Figure 1: Flow chart for the selection of ovarian cancer cases in the Nurses’ Health Study (NHS) and NHSII, limited to ovarian cancer diagnosis, available tissue, available data on parental smoke exposure, and successful multi ...
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Other · June 3, 2024
<p>Supplemental Table 2: Age-standardized baseline characteristics by parental smoking during childhood or adolescence, NHS (1982) and NHSII (1999)</p> ...
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Other · June 3, 2024
<p>Supplemental Table 10: Hazard ratios and 95% confidence intervals between smoking and ovarian cancer risk by tumor immune infiltration of immunoglobulins among Type II tumors, NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Table 7: Hazard ratios and 95% confidence intervals between smoking and ovarian cancer risk by tumor immune infiltration of B cells, NHS and NHSII</p> ...
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Other · June 3, 2024
<p>Supplemental Table 3: Characteristics of women with ovarian cancer in NHS and NHSII, overall and who had tumor tissue on the TMAs and information about lifetime cigarette smoke exposure</p> ...
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Other · June 3, 2024
<p>Supplemental Table 5: Odds ratios and 95% confidence intervals for positivity of tumor immune infiltration of various types of B cells and immunoglobulins by smoking status among cases in NHS only</p> ...
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Other · June 3, 2024
<div>AbstractBackground:<p>Cigarette smoke exposure has been linked to systemic immune dysfunction, including for B-cell and immunoglobulin (Ig) production, and poor outcomes in patients with ovarian cancer. No study has evaluated the i ...
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Other · May 17, 2024
<div>AbstractBackground:<p>Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ...
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Other · May 17, 2024
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · May 17, 2024
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · May 17, 2024
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · May 17, 2024
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · May 17, 2024
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · May 17, 2024
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · May 17, 2024
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · May 17, 2024
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · May 17, 2024
<div>AbstractBackground:<p>Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ...
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Other · May 17, 2024
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · May 17, 2024
<div>AbstractBackground:<p>Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ...
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Other · May 17, 2024
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · May 17, 2024
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · May 17, 2024
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · May 17, 2024
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · May 17, 2024
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · May 17, 2024
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · May 17, 2024
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · May 17, 2024
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · May 17, 2024
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · May 17, 2024
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · May 17, 2024
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Journal ArticleLife (Basel) · February 29, 2024
Immuno-oncology has traditionally focused on conventional MHC-restricted αβ T cells. Yet, unconventional γδ T cells, which kill tumor cells in an MHC-unrestricted manner, display characteristics of effector activity and stemness without exhaustion and are ...
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Journal ArticleMol Carcinog · January 2024
Head and neck squamous cell carcinomas (HNSCC) remain a poorly understood disease clinically and immunologically. HPV is a known risk factor of HNSCC associated with better outcome, whereas HPV-negative HNSCC are more heterogeneous in outcome. Gene express ...
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Journal ArticleRes Sq · December 14, 2023
Mounting effective immunity against pathogens and tumors relies on the successful metabolic programming of T cells by extracellular fatty acids1-3. During this process, fatty-acid-binding protein 5 (FABP5) imports lipids that fuel mitochondrial respiration ...
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Other · November 20, 2023
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · November 20, 2023
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · November 20, 2023
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · November 20, 2023
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · November 20, 2023
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · November 20, 2023
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · November 20, 2023
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · November 20, 2023
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · November 20, 2023
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · November 20, 2023
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · November 20, 2023
<div>AbstractBackground:<p>Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ...
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Journal ArticleImmunity · November 14, 2023
Dimeric IgA (dIgA) can move through cells via the IgA/IgM polymeric immunoglobulin receptor (PIGR), which is expressed mainly on mucosal epithelia. Here, we studied the ability of dIgA to target commonly mutated cytoplasmic oncodrivers. Mutation-specific d ...
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Journal ArticleBrain, behavior, and immunity · November 2023
BackgroundDepression is associated with a higher ovarian cancer risk. Prior work suggests that depression can lead to systemic immune suppression, which could potentially alter the anti-tumor immune response.MethodsWe evaluated the associ ...
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Journal ArticleCancers (Basel) · October 10, 2023
BACKGROUND: We aimed to determine the prognostic value of an immunoscore reflecting CD3+ and CD8+ T cell density estimated from real-world transcriptomic data of a patient cohort with advanced malignancies treated with immune checkpoint inhibitors (ICIs) i ...
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Journal ArticleClin Cancer Res · October 2, 2023
PURPOSE: Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal an ...
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Other · October 2, 2023
<div>AbstractPurpose:<p>Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of dur ...
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Journal ArticleBlood Adv · September 26, 2023
The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and 29 932 CD3+CD4+ and CD26-/CD7- lymphocytes from the peripheral blood of 7 patients with CT ...
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Journal ArticleCancer Med · September 2023
BACKGROUND: Aspirin use has been associated with reduced ovarian cancer risk, yet the underlying biological mechanisms are not fully understood. To gain mechanistic insights, we assessed the association between prediagnosis low and regular-dose aspirin use ...
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Journal ArticleNat Commun · July 26, 2023
Interest in spatial omics is on the rise, but generation of highly multiplexed images remains challenging, due to cost, expertise, methodical constraints, and access to technology. An alternative approach is to register collections of whole slide images (W ...
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Journal ArticleInt J Radiat Oncol Biol Phys · July 15, 2023
PURPOSE: We hypothesized that concurrent ipilimumab with chemoradiationtherapy (chemoRT) followed by maintenance nivolumab would be safe for patients with unresectable stage III non-small cell lung cancer (NSCLC). We aimed to assess the safety (phase 1) an ...
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Journal ArticleCancer Immunol Immunother · June 2023
Radiation therapy (RT) can prime and boost systemic anti-tumor effects via STING activation, resulting in enhanced tumor antigen presentation and antigen recognition by T cells. It is increasingly recognized that optimal anti-tumor immune responses benefit ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · June 1, 2023
BACKGROUND: Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ovarian tumor immune microenvironm ...
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Journal ArticleGynecol Oncol · June 2023
OBJECTIVE: To demonstrate that shared antibody responses in endometriosis and endometriosis-associated ovarian cancer spontaneously antagonize malignant progression and can be leveraged to develop future immunotherapies. METHODS: B cells from cyopreserved ...
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Other · June 1, 2023
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · June 1, 2023
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · June 1, 2023
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · June 1, 2023
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · June 1, 2023
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · June 1, 2023
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · June 1, 2023
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · June 1, 2023
<div>AbstractBackground:<p>Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ...
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Other · June 1, 2023
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · June 1, 2023
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · June 1, 2023
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · May 22, 2023
<p>TIMEx scores for the Immune gene signature among the 15 patients classified into the Hypoxia, Mixture and Immune subgroups.</p> ...
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Other · May 22, 2023
<p>(A, B) Heatmap of molecular subgroups in two different HNSCC datasets (A) TCGA and (B) CPTAC. RNA expression data was z-normalized, each row represents a single gene in the hypoxia-immune signature gene list, each column represents a patie ...
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Other · May 22, 2023
<p>Molecular classification and validation of hypoxia-immune signature in HNSCC. <b>A,</b> Heatmap of molecular subgroups in the Moffitt (<i>n</i> = 228) HNSCC cohort. RNA expression data were z-normalized, each row re ...
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Other · May 22, 2023
<p>Hypoxia subgroup has an enrichment of EGFR pathway. Pearson correlation coefficient for the TIMEx scores for the EGFR pathway and the Hypoxia gene signature among the TCGA (<b>A</b>), CPTAC (<b>B</b>), and Moffitt ( ...
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Other · May 22, 2023
<p>GSEA of hallmark pathways in TCGA and Moffitt cohorts. TCGA (<b>A–C</b>) and Moffitt head and neck squamous cell carcinoma (<b>D–F</b>) cohorts. The gene expressions were compared for pathways enriched in: (<b> ...
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Other · May 22, 2023
<p>Protein network analysis of core-enriched genes within the hypoxia signature and TGF-β signaling from GSEA analysis. Clustering was performed using the STRING database. Three main clusters are depicted: hypoxia (blue color), TGF-β (green c ...
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Other · May 22, 2023
<p>Cetuximab treatment benefits Hypoxia subgroup. <b>A,</b> Heatmap of gene expression data from pre- and post-cetuximab (CTX) treated patient samples. RNA expression data (GSE109756) was z-normalized, each row represents a single ...
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Other · May 22, 2023
<p>Protein network analysis of core-enriched genes within the hypoxia signature and TGF-β signaling from GSEA analysis. Clustering was performed using the STRING database. Three main clusters are depicted: hypoxia (blue color), TGF-β (green c ...
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Other · May 22, 2023
<p>Hypoxia subgroup has an enrichment of EGFR pathway. Pearson correlation coefficient for the TIMEx scores for the EGFR pathway and the Hypoxia gene signature among the TCGA (<b>A</b>), CPTAC (<b>B</b>), and Moffitt ( ...
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Other · May 22, 2023
<p>(A-C) Clinical Proteomic Tumor Analysis Consortium head and neck squamous cell carcinoma cohort. The gene expressions were compared for pathways enriched in: (A) Immune vs Hypoxia. Red: enriched in Immune, Blue: enriched in Hypoxia. (B) Im ...
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Other · May 22, 2023
<p>(A, B) Representative mIHC images showing staining of nuclei (blue), tumor cell (orange - PCK) and selected immune checkpoint markers in each molecular subgroup. (A) Images show four lymphoid markers - CD3+ T-cells (Green), CD8+ cytotoxic ...
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Other · May 22, 2023
<p>Heatmap of molecular subgroups in MCC18754 (n=48). RNA expression data was z-normalized, each row represents a single gene in the Hypoxia-Immune signature gene list, each column represents a patient sample. Samples were reordered according ...
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Other · May 22, 2023
<p>(A-C) Clinical Proteomic Tumor Analysis Consortium head and neck squamous cell carcinoma cohort. The gene expressions were compared for pathways enriched in: (A) Immune vs Hypoxia. Red: enriched in Immune, Blue: enriched in Hypoxia. (B) Im ...
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Other · May 22, 2023
<p>(A, B) Heatmap of molecular subgroups in two different HNSCC datasets (A) TCGA and (B) CPTAC. RNA expression data was z-normalized, each row represents a single gene in the hypoxia-immune signature gene list, each column represents a patie ...
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Other · May 22, 2023
<p>Molecular classification and validation of hypoxia-immune signature in HNSCC. <b>A,</b> Heatmap of molecular subgroups in the Moffitt (<i>n</i> = 228) HNSCC cohort. RNA expression data were z-normalized, each row re ...
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Other · May 22, 2023
<p>Heatmap of molecular subgroups in MCC18754 (n=48). RNA expression data was z-normalized, each row represents a single gene in the Hypoxia-Immune signature gene list, each column represents a patient sample. Samples were reordered according ...
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Other · May 22, 2023
<p>(A, B) Representative mIHC images showing staining of nuclei (blue), tumor cell (orange - PCK) and selected immune checkpoint markers in each molecular subgroup. (A) Images show four lymphoid markers - CD3+ T-cells (Green), CD8+ cytotoxic ...
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Other · May 22, 2023
<div><p>Head and neck squamous cell carcinoma (HNSCC) has one of the most hypoxic and immunosuppressive tumor microenvironments (TME) among solid tumors. However, there is no proven therapeutic strategy to remodel the TME to be less hyp ...
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Other · May 22, 2023
<p>Hypoxia subgroup has immunosuppressive TME. Boxplots showing cell counts distribution of different immune markers CAIX<sup>+</sup> cells representing hypoxia marker (<b>A</b>), CD3<sup>+</sup> T cells (& ...
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Other · May 22, 2023
<p>GSEA of hallmark pathways in TCGA and Moffitt cohorts. TCGA (<b>A–C</b>) and Moffitt head and neck squamous cell carcinoma (<b>D–F</b>) cohorts. The gene expressions were compared for pathways enriched in: (<b> ...
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Other · May 22, 2023
<p>Hypoxia subgroup has immunosuppressive TME. Boxplots showing cell counts distribution of different immune markers CAIX<sup>+</sup> cells representing hypoxia marker (<b>A</b>), CD3<sup>+</sup> T cells (& ...
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Other · May 22, 2023
<p>Cetuximab treatment benefits Hypoxia subgroup. <b>A,</b> Heatmap of gene expression data from pre- and post-cetuximab (CTX) treated patient samples. RNA expression data (GSE109756) was z-normalized, each row represents a single ...
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Other · May 22, 2023
<p>Supplementary Table S8. Hypoxia-Immune classification of Schmitz et al., window-of-opportunity trial (GSE109756)</p> ...
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Other · May 22, 2023
<p>Supplementary Table S8. Hypoxia-Immune classification of Schmitz et al., window-of-opportunity trial (GSE109756)</p> ...
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Other · May 22, 2023
<p>TIMEx scores for the Immune gene signature among the 15 patients classified into the Hypoxia, Mixture and Immune subgroups.</p> ...
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Other · May 4, 2023
<p>(A-C) Clinical Proteomic Tumor Analysis Consortium head and neck squamous cell carcinoma cohort. The gene expressions were compared for pathways enriched in: (A) Immune vs Hypoxia. Red: enriched in Immune, Blue: enriched in Hypoxia. (B) Im ...
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Other · May 4, 2023
<p>(A, B) Heatmap of molecular subgroups in two different HNSCC datasets (A) TCGA and (B) CPTAC. RNA expression data was z-normalized, each row represents a single gene in the hypoxia-immune signature gene list, each column represents a patie ...
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Other · May 4, 2023
<p>Protein network analysis of core-enriched genes within the hypoxia signature and TGF-β signaling from GSEA analysis. Clustering was performed using the STRING database. Three main clusters are depicted: hypoxia (blue color), TGF-β (green c ...
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Other · May 4, 2023
<p>TIMEx scores for the Immune gene signature among the 15 patients classified into the Hypoxia, Mixture and Immune subgroups.</p> ...
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Other · May 4, 2023
<p>Heatmap of molecular subgroups in MCC18754 (n=48). RNA expression data was z-normalized, each row represents a single gene in the Hypoxia-Immune signature gene list, each column represents a patient sample. Samples were reordered according ...
Full textCite
Other · May 4, 2023
<p>(A, B) Representative mIHC images showing staining of nuclei (blue), tumor cell (orange - PCK) and selected immune checkpoint markers in each molecular subgroup. (A) Images show four lymphoid markers - CD3+ T-cells (Green), CD8+ cytotoxic ...
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Other · May 4, 2023
<p>(A-C) Clinical Proteomic Tumor Analysis Consortium head and neck squamous cell carcinoma cohort. The gene expressions were compared for pathways enriched in: (A) Immune vs Hypoxia. Red: enriched in Immune, Blue: enriched in Hypoxia. (B) Im ...
Full textCite
Other · May 4, 2023
<p>Heatmap of molecular subgroups in MCC18754 (n=48). RNA expression data was z-normalized, each row represents a single gene in the Hypoxia-Immune signature gene list, each column represents a patient sample. Samples were reordered according ...
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Other · May 4, 2023
<p>TIMEx scores for the Immune gene signature among the 15 patients classified into the Hypoxia, Mixture and Immune subgroups.</p> ...
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Other · May 4, 2023
<p>Protein network analysis of core-enriched genes within the hypoxia signature and TGF-β signaling from GSEA analysis. Clustering was performed using the STRING database. Three main clusters are depicted: hypoxia (blue color), TGF-β (green c ...
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Other · May 4, 2023
<p>(A, B) Representative mIHC images showing staining of nuclei (blue), tumor cell (orange - PCK) and selected immune checkpoint markers in each molecular subgroup. (A) Images show four lymphoid markers - CD3+ T-cells (Green), CD8+ cytotoxic ...
Full textCite
Other · May 4, 2023
<p>(A, B) Heatmap of molecular subgroups in two different HNSCC datasets (A) TCGA and (B) CPTAC. RNA expression data was z-normalized, each row represents a single gene in the hypoxia-immune signature gene list, each column represents a patie ...
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Other · May 4, 2023
<div>Abstract<p>Head and neck squamous cell carcinoma (HNSCC) has one of the most hypoxic and immunosuppressive tumor microenvironments (TME) among solid tumors. However, there is no proven therapeutic strategy to remodel the TME to be ...
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Other · May 4, 2023
<p>Supplementary Table S8. Hypoxia-Immune classification of Schmitz et al., window-of-opportunity trial (GSE109756)</p> ...
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Other · May 4, 2023
<p>Supplementary Table S8. Hypoxia-Immune classification of Schmitz et al., window-of-opportunity trial (GSE109756)</p> ...
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Journal ArticleCancer Res Commun · May 2023
UNLABELLED: Head and neck squamous cell carcinoma (HNSCC) has one of the most hypoxic and immunosuppressive tumor microenvironments (TME) among solid tumors. However, there is no proven therapeutic strategy to remodel the TME to be less hypoxic and proinfl ...
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Journal ArticleSci Immunol · April 28, 2023
The networks of transcription factors (TFs) that control intestinal-resident memory CD8+ T (TRM) cells, including multipotency and effector programs, are poorly understood. In this work, we investigated the role of the TF Bcl11b in TRM cells during infecti ...
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Other · April 12, 2023
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · April 12, 2023
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · April 12, 2023
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · April 12, 2023
<p>Supplemental Table 4 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by tumor and participant characteristics</p> ...
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Other · April 12, 2023
<div>AbstractBackground:<p>Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ...
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Other · April 12, 2023
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · April 12, 2023
<p>Supplemental Table 5 shows beta binomial models, odds ratios and 95% confidence intervals for marker positivity in the tumor, by population characteristics</p> ...
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Other · April 12, 2023
<p>Supplemental Table 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors</p> ...
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Other · April 12, 2023
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · April 12, 2023
<p>Supplemental Figure 1 provides representative images from the T cell panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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Other · April 12, 2023
<p>Supplemental Figure 2 provides representative images from the immune checkpoint panel for high-grade serous, endometrioid, clear cell, and mucinous tumors.</p> ...
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ConferenceCancer Research · April 4, 2023
AbstractVarious forms of distress, most notably depression, increase ovarian cancer risk. Prior work suggests depression can lead to systemic immune suppression; moreover, after ovarian cancer diagnosis, ong ...
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ConferenceCancer Research · April 4, 2023
AbstractIntroduction: An estimated 38 million US women currently use contraception, a critical component of women’s health. Yet, the impact of changing contraceptive types and patterns of use on ovarian canc ...
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ConferenceCancer Research · April 4, 2023
AbstractIntroduction: Breastfeeding is associated with decreased ovarian cancer risk, yet the biological mechanisms are not fully understood. We conducted an agnostic investigation of tumor immune profiles t ...
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Other · March 31, 2023
Supplementary Data from Tumor Expression Quantitative Trait Methylation Screening Reveals Distinct CpG Panels for Deconvolving Cancer Immune Signatures ...
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Other · March 31, 2023
Supplementary Figure from Tumor Expression Quantitative Trait Methylation Screening Reveals Distinct CpG Panels for Deconvolving Cancer Immune Signatures ...
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Other · March 31, 2023
Supplementary Data from Tumor Expression Quantitative Trait Methylation Screening Reveals Distinct CpG Panels for Deconvolving Cancer Immune Signatures ...
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Other · March 31, 2023
Supplementary Figure from Tumor Expression Quantitative Trait Methylation Screening Reveals Distinct CpG Panels for Deconvolving Cancer Immune Signatures ...
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Other · March 31, 2023
<div>Abstract<p>DNA methylation signatures in tumors could serve as reliable biomarkers that are accessible in archival tissues for tracking the epigenetic dynamics shaped by both cancer cells and the tumor microenvironment. However, gi ...
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Other · March 31, 2023
<div>Abstract<p>DNA methylation signatures in tumors could serve as reliable biomarkers that are accessible in archival tissues for tracking the epigenetic dynamics shaped by both cancer cells and the tumor microenvironment. However, gi ...
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Journal ArticleCancers (Basel) · March 14, 2023
Although Ipilimumab (anti-CTLA-4) is FDA-approved for stage III/IV melanoma adjuvant treatment, it is not used clinically in first-line therapy, given the superior relapse-free survival (RFS)/toxicity benefits of anti-PD-1 therapy. However, it is important ...
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Journal ArticleJ Immunother Cancer · February 2023
BACKGROUND: Tumor intracellular programmed cell death ligand-1 (PDL1) mediates pathologic signals that regulate clinical treatment responses distinctly from surface-expressed PDL1 targeted by αPDL1 immune checkpoint blockade antibodies. METHODS: We perform ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · January 9, 2023
BACKGROUND: Exposure to cigarette smoke, particularly in early life, is modestly associated with ovarian cancer risk and may impact systemic immunity and the tumor immune response. However, no studies have evaluated whether cigarette smoke exposure impacts ...
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Journal ArticleSemin Immunol · January 2023
Immuno-oncology has traditionally focused on the cellular arm of the adaptive immune response, while attributing tumor-promoting activity to humoral responses in tumor-bearing hosts. This view stems from mouse models that do not necessarily recapitulate th ...
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Journal ArticleCancer Immunol Res · December 2, 2022
Fragility of regulatory T (Treg) cells manifested by the loss of neuropilin-1 (NRP1) and expression of IFNγ undermines the immune suppressive functions of Treg cells and contributes to the success of immune therapies against cancers. Intratumoral Treg cell ...
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Journal ArticleImmunol Invest · November 2022
CAR T-cell therapy has transformed the treatment of hematological malignancies of the B cell lineage. However, the quest to fulfil the same promise for solid tumors is still in its infancy. This review summarizes some of the challenges that the field is tr ...
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Journal ArticleCancer Cell · October 10, 2022
Activation of unfolded protein responses (UPRs) in cancer cells undergoing endoplasmic reticulum (ER) stress promotes survival. However, how UPR in tumor cells impacts anti-tumor immune responses remains poorly described. Here, we investigate the role of t ...
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Journal ArticleProc Natl Acad Sci U S A · October 4, 2022
Limiting CD4+ T cell responses is important to prevent solid organ transplant rejection. In a mouse model of costimulation blockade-dependent cardiac allograft tolerance, we previously reported that alloreactive CD4+ conventional T cells (Tconvs) develop d ...
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Journal ArticleSTAR Protoc · September 16, 2022
Understanding the heterogenicity of tumor-infiltraing lymphocyte (TIL) populations and the immunobiology in human cancer is a key to establish efficient immunotherapies. Here, we have established a protocol for the characterization of CD8+ TILs in tumors b ...
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Journal ArticleCancer Discov · August 5, 2022
Much work has been done to reduce cancer immunosuppression through inhibiting soluble proteins, surface molecules, and suppressive cells. This article shows an important role for the lipid lysophosphatidic acid, whose suppression shows promise as a novel c ...
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Journal ArticleMol Cancer Ther · July 5, 2022
Although chimeric antigen receptor (CAR)-expressing T cells have proven success in hematologic malignancies, their effectiveness in solid tumors has been largely unsuccessful thus far. We found that some olfactory receptors are expressed in a variety of so ...
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Journal ArticleCancer Res · June 6, 2022
UNLABELLED: BRCA1-mediated homologous recombination is an important DNA repair mechanism that is the target of FDA-approved PARP inhibitors, yet details of BRCA1-mediated functions remain to be fully elucidated. Similarly, immune checkpoint molecules are t ...
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Journal ArticleJ Transl Med · June 3, 2022
BACKGROUND: We hypothesized that a gender difference in clinical response may exist to adjuvant CTLA4 blockade with ipilimumab versus high-dose IFNα (HDI). We investigated differences in candidate immune biomarkers in the circulation and tumor microenviron ...
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Journal ArticleJ Immunother Cancer · June 2022
BACKGROUND: T cell receptor (TCR) signaling profile is a fundamental property that underpins both adaptive and innate immunity in the host. Despite its potential clinical relevance, the TCR repertoire in peripheral blood has not been thoroughly explored fo ...
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Journal ArticleCancer Cell · May 9, 2022
Despite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of tumor recognition in ovarian cancer-infiltrating T cells are primarily restricted to tis ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · May 4, 2022
BACKGROUND: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. METHODS: The current study investigated racial differences in the tumor immu ...
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Journal ArticleInt J Mol Sci · May 4, 2022
The interaction between tumor surface-expressed PDL1 and immune cell PD1 for the evasion of antitumor immunity is well established and is targeted by FDA-approved anti-PDL1 and anti-PD1 antibodies. Nonetheless, recent studies highlight the immunopathogenic ...
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Journal ArticleCancer Res · May 3, 2022
UNLABELLED: DNA methylation signatures in tumors could serve as reliable biomarkers that are accessible in archival tissues for tracking the epigenetic dynamics shaped by both cancer cells and the tumor microenvironment. However, given the ultrahigh dimens ...
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Journal ArticleCancer Discov · May 2, 2022
ABSTRACT: Cutaneous T-cell lymphoma (CTCL) is a rare cancer of skin-homing T cells. A subgroup of patients develops large cell transformation with rapid progression to an aggressive lymphoma. Here, we investigated the transformed CTCL (tCTCL) tumor ecosyst ...
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ConferenceThe Journal of Immunology · May 1, 2022
AbstractThe role of humoral responses in endometrial cancer remains insufficiently investigated. Using a cohort of 107 patients with different histological subtypes of endometrial carcinoma, we report that c ...
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ConferenceThe Journal of Immunology · May 1, 2022
AbstractDespite repeated associations between T-cell infiltration and patient outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that hallmarks of tumor recognition in ovaria ...
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ConferenceThe Journal of Immunology · May 1, 2022
AbstractChimeric antigen receptor (CAR) T cells have been successful for hematological malignancies, but so far showed limited efficiency against solid tumors. Olfactory receptors are expressed in a variety ...
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Journal ArticleGenome Med · March 29, 2022
BACKGROUND: Recent studies show that human gut microbial composition can determine whether a patient is a responder or non-responder to immunotherapy but have not identified a common microbial signal shared by responding patients. The functional relationsh ...
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Journal ArticleCancer Res · March 1, 2022
UNLABELLED: Recent studies suggest that B cells could play an important role in the tumor microenvironment. However, the role of humoral responses in endometrial cancer remains insufficiently investigated. Using a cohort of 107 patients with different hist ...
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Journal ArticleImmunity · January 11, 2022
The immune checkpoint receptor PD-1 on T follicular helper (Tfh) cells promotes Tfh:B cell interactions and appropriate positioning within tissues. Here, we examined the impact of regulation of PD-1 expression by the genomic organizer SATB1 on Tfh cell dif ...
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Journal ArticleLeuk Lymphoma · January 2022
Sézary syndrome (SS) is a rare and aggressive leukemic variant of cutaneous T-cell lymphoma, with a median overall survival (OS) rate of 2-4 years. Few studies have described the clinical outcome of SS patients since 2012. We retrospectively analyzed 70 pa ...
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ConferenceCancer Epidemiology, Biomarkers & Prevention · January 1, 2022
AbstractA survival benefit has been consistently observed for tumor infiltrating lymphocytes (TILs) among ovarian cancer patients; however, prior studies consist of predominantly white women and little work ...
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Journal ArticlePLoS One · 2022
The distribution of Endometrial Cancer (EC)-related deaths is uneven among the morphologic subtypes of EC. Serous Cancer (SC) makes 10% of all EC and accounts for 40% of EC-related deaths. We investigated expression of selected genes involved in epigenetic ...
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Journal ArticleJ Immunother Cancer · January 2022
BACKGROUND: Melanoma of unknown primary (MUP) represents a poorly understood group of patients both clinically and immunologically. We investigated differences in prognosis and candidate immune biomarkers in patients with unknown compared with those with k ...
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Journal ArticleJ Immunother Cancer · January 2022
BACKGROUND: T cell immunoglobulin and mucin domain containing-3 (TIM-3) blocking antibodies are currently being evaluated in clinical trials for solid and hematological malignancies. Despite its identification on T cells, TIM-3 is predominantly expressed b ...
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Journal ArticleFront Oncol · 2022
Optimal management of locally advanced vaginal mucosal melanoma is poorly understood because of its rarity and unique biology. Patients have a poor prognosis despite aggressive management approaches including pelvic exenteration and adjuvant radiation that ...
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ConferenceJournal for ImmunoTherapy of Cancer · November 2021
BackgroundSex differences in tumor immunity and response to immunotherapy were shown in murine models and descriptive analyses from recent clinical trials. We recently reported that female gender is a favorable pr ...
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ConferenceJournal for ImmunoTherapy of Cancer · November 2021
BackgroundWe recently reported data supporting the unknown primary status as a potentially distinct prognostic group among high-risk melanoma patients treated with ipilimumab and high dose interferon-alfa (HDI) in ...
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Journal ArticleCancer Cell · October 11, 2021
Tumor-infiltrating B cells complement T cell-mediated antitumor immunity. A panel of experts share their views on the complexity of B cells within the tumor microenvironment, the variety of mechanisms by which these cells control tumor growth, their organi ...
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Journal ArticleNat Rev Urol · September 2021
The advent of immune checkpoint inhibition (ICI) has transformed the treatment paradigm for bladder cancer. However, despite the success of ICI in other tumour types, the majority of ICI-treated patients with bladder cancer failed to respond. The lack of e ...
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Journal ArticleNat Med · August 2021
Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer. We conducted a single-arm open-label phase 1 trial ( NCT03215810 ) of TILs adm ...
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ConferenceJournal of Clinical Oncology · May 20, 2021
e17538 Background: Despite evidence that ovarian cancer (OC) is an immunogenic disease, single-agent checkpoint inhibitors have shown limited response. A clinical trial was conducted evaluating dose-dense paclitaxel and pembroliz ...
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ConferenceJournal of Clinical Oncology · May 20, 2021
e21584 Background: Predicting immune-related adverse events (irAEs) resulting from immune checkpoint inhibitors (ICIs) as well as the likelihood of clinical benefit is an area of great interest. irAEs have been associated with cl ...
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Journal ArticleBlood · May 13, 2021
Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory large B-cell lymphoma (LBCL). This study evaluated whether immune dysregulation, present before CAR T-cell therapy, was associated with treatme ...
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Journal ArticleMol Ther · April 7, 2021
HER2 breast cancer (BC) remains a significant problem in patients with locally advanced or metastatic BC. We investigated the relationship between T helper 1 (Th1) immune response and the proteasomal degradation pathway (PDP), in HER2-sensitive and -resist ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · April 2021
BACKGROUND: Chronic inflammation is a well-established mechanism of ovarian carcinogenesis; however, the specific immunogenic processes influencing ovarian tumor development remain unclear. In a case-control study nested within the Nurses' Health Study (NH ...
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Journal ArticleJ Immunother Cancer · April 2021
BACKGROUND: Anti-programmed death-ligand 1 (αPD-L1) immunotherapy is approved to treat bladder cancer (BC) but is effective in <30% of patients. Interleukin (IL)-2/αIL-2 complexes (IL-2c) that preferentially target IL-2 receptor β (CD122) augment CD8+ anti ...
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Journal ArticleNature · March 2021
Most ovarian cancers are infiltrated by prognostically relevant activated T cells1-3, yet exhibit low response rates to immune checkpoint inhibitors4. Memory B cell and plasma cell infiltrates have previously been associated with better outcomes in ovarian ...
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ConferenceJournal of Clinical Oncology · February 20, 2021
466 Background: Adaptive anti-tumor immunity can be orchestrated by lymph node-like immune cell aggregates within the tumor microenvironment (TME) called tertiary lymphoid structures (TLSs). TLSs are postulated to be the gateway ...
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Journal ArticleInt J Radiat Oncol Biol Phys · February 1, 2021
PURPOSE: Consolidative thoracic radiation therapy (TRT) has been shown to improve outcomes for patients with extensive stage small cell lung cancer. We hypothesized that the addition of ipilimumab (IPI) and nivolumab (NIVO) after TRT would improve outcomes ...
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Journal ArticleJ Clin Invest · February 1, 2021
Cutaneous T cell lymphoma (CTCL) has a poorly understood etiology and no known cure. Using conditional knockout mice, we found that ablation of the genomic organizer special AT-rich sequence-binding protein 1 (Satb1) caused malignant transformation of matu ...
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Journal ArticleMol Carcinog · February 2021
Prognosis for patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) remains poor. Development of more effective and less toxic targeted therapies is necessary for HNSCC patients. Checkpoint kinase 1 (CHK1) plays a vital ro ...
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Journal ArticleFront Immunol · 2021
Recent years have witnessed a dramatic rise in interest towards cancer epitopes in general and particularly neoepitopes, antigens that are encoded by somatic mutations that arise as a consequence of tumorigenesis. There is also an interest in the specific ...
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Journal ArticleFront Immunol · 2021
There is emerging evidence that the adaptive anti-tumor activity may be orchestrated by secondary lymphoid organ-like aggregates residing in the tumor microenvironment. Known as tertiary lymphoid structures, these lymphoid aggregates serve as key outposts ...
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Journal ArticleComput Struct Biotechnol J · 2021
Cell type classification is an important problem in cancer research, especially with the advent of single cell technologies. Correctly identifying cells within the tumor microenvironment can provide oncologists with a snapshot of how a patient's immune sys ...
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Journal ArticleCancer Res · November 15, 2020
The IL2 receptor (IL2R) is an attractive cancer immunotherapy target that controls immunosuppressive T regulatory cells (Treg) and antitumor T cells. Here we used IL2Rβ-selective IL2/anti-IL2 complexes (IL2c) to stimulate effector T cells preferentially in ...
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Journal ArticleInt J Cancer · October 15, 2020
The microenvironment of pancreatic cancer adenocarcinoma (PDAC) is highly desmoplastic with distinct tumor-restraining and tumor-promoting fibroblast subpopulations. Re-education rather than indiscriminate elimination of these fibroblasts has emerged as a ...
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Journal ArticleCell Metab · September 1, 2020
Dysregulated metabolism is a key driver of maladaptive tumor-reactive T lymphocytes within the tumor microenvironment. Actionable targets that rescue the effector activity of antitumor T cells remain elusive. Here, we report that the Sirtuin-2 (Sirt2) NAD+ ...
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Journal ArticleInt J Gynecol Pathol · September 2020
Management options are limited in advanced or recurrent cervical carcinoma. The Food and Drug Administration has recently approved programed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) inhibitors for the treatment of advanced PD-L1 positive cervical cancer. We ...
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Journal ArticleCancer Epidemiol Biomarkers Prev · September 2020
BACKGROUND: MUC16 is a mucin marker that is frequently mutated in melanoma, but whether MUC16 mutations could be useful as a surrogate biomarker for tumor mutation burden (TMB) remains unclear. METHODS: This study rigorously evaluates the MUC16 mutation as ...
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Journal ArticleScience · August 21, 2020
Gamma delta (γδ) T cells infiltrate most human tumors, but current immunotherapies fail to exploit their in situ major histocompatibility complex-independent tumoricidal potential. Activation of γδ T cells can be elicited by butyrophilin and butyrophilin-l ...
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ConferenceCancer Research · August 15, 2020
AbstractStudy Objectives: A hallmark of tumor infiltrating lymphocytes (TIL) in melanoma is the potential for a complete response (CR) which can last for decades. This long-lived effect is attributed to pers ...
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ConferenceCancer Research · August 15, 2020
AbstractPancreatic ductal adenocarcinoma (PDAC) is a recalcitrant and lethal disease with an overall 5-year survival rate of less than 8%. The abundance and heterogeneity of cancer-associated fibroblasts (CA ...
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Journal ArticleJ Leukoc Biol · June 2020
Discussion on the role of Kindlin-3 in the capacity of nonclassical monocytes to prevent malignant colonization of vascularized tissues by ensuring effective endothelial adhesion. ...
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Journal ArticleSemin Immunol · June 2020
Solid cancers progress from primordial lesions through complex interactions between tumor-promoting and anti-tumor immune cell types, ultimately leading to the orchestration of humoral and T cell adaptive immune responses, albeit in an immunosuppressive en ...
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Journal ArticleJ Immunother Cancer · June 2020
Despite regulatory approval of several immune-based treatments for cancer in the past decade, a number of barriers remain to be addressed in order to fully harness the therapeutic potential of the immune system and provide benefits for patients with cancer ...
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Journal ArticleImmunity · April 14, 2020
The primary mechanisms supporting immunoregulatory polarization of myeloid cells upon infiltration into tumors remain largely unexplored. Elucidation of these signals could enable better strategies to restore protective anti-tumor immunity. Here, we invest ...
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Journal ArticleJ Clin Invest · April 1, 2020
Tumor-associated macrophages (TAMs) represent the most abundant hematopoietic cell type in the solid tumor microenvironment. TAMs drive T cell inhibition, promote angiogenesis, and produce tumor growth factors. Although they can paradoxically exert antitum ...
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Journal ArticleClin Cancer Res · March 15, 2020
PURPOSE: Patients with head and neck squamous cell carcinoma (HNSCC) who actively smoke during treatment have worse survival compared with never-smokers and former-smokers. We hypothesize the poor prognosis in tobacco smokers with HNSCC is, at least in par ...
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Journal ArticleJ Immunol · December 15, 2019
Tumor-associated macrophages are major contributors to malignant progression and resistance to immunotherapy, but the mechanisms governing their differentiation from immature myeloid precursors remain incompletely understood. In this study, we demonstrate ...
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Journal ArticleCancer Res · October 1, 2019
Myeloid-derived suppressor cells (MDSC) represent a primary mechanism of immune evasion in tumors and have emerged as a major obstacle for cancer immunotherapy. The immunoinhibitory activity of MDSC is tightly regulated by the tumor microenvironment and oc ...
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Journal ArticleNat Commun · August 15, 2019
An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
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Journal ArticleJ Clin Invest · July 29, 2019
Pancreatic ductal adenocarcinoma is projected to become the second leading cause of cancer-related death and is largely resistant to immunotherapies. The tumor microenvironment, largely composed of heterogeneous myeloid cells, creates a physical, metabolic ...
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Journal ArticleBMC Cancer · July 19, 2019
BACKGROUND: The rapid development of single-cell RNA sequencing (scRNA-seq) provides unprecedented opportunities to study the tumor ecosystem that involves a heterogeneous mixture of cell types. However, the majority of previous and current studies related ...
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Journal ArticleCancer Cell · June 10, 2019
We investigated the role of chemokines in regulating T cell accumulation in solid tumors. CCL5 and CXCL9 overexpression was associated with CD8+ T cell infiltration in solid tumors. T cell infiltration required tumor cell-derived CCL5 and was amplified by ...
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ConferenceJournal of Clinical Oncology · May 20, 2019
TPS5596 Background: There is no consistent recommendation for management of metastatic cervical cancer beyond first line therapy with chemotherapy and bevacizumab. Pembrolizumab is now approved for PD-L1 positive or MSI-H/dMMR me ...
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Journal ArticleJCO Clin Cancer Inform · April 2019
PURPOSE: Early-stage cancers are routinely treated with surgery followed by radiotherapy (SR). Radiotherapy before surgery (RS) has been widely ignored for some cancers. We evaluate overall survival (OS) and disease-free survival (DFS) with SR and RS for d ...
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Journal ArticleFront Phys · April 2019
Cancer photomedicine offers unique mechanisms for inducing local tumor damage with the potential to stimulate local and systemic anti-tumor immunity. Optically-active nanomedicine offers these features as well as spatiotemporal control of tumor-focused dru ...
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Journal ArticleNat Commun · March 20, 2019
Understanding the intrinsic mediators that render CD8+ T cells dysfunctional in the tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report that C/EBP homologous protein (Chop), a downstream sensor of sever ...
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ConferenceCancer Research · February 15, 2019
AbstractAlthough the role of estrogen signaling in the progression of a subset of breast tumors has been underscored by the clinical use of Estrogen Receptor antagonists, how estrogens impact protective anti ...
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Journal ArticleOncoimmunology · 2019
Ovarian cancer is frequently diagnosed as peritoneal carcinomatosis. Unlike other tumor locations, the peritoneal cavity is commonly exposed to gut-breaching and ascending genital microorganisms and has a unique immune environment. IL-33 is a local cytokin ...
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Journal ArticlePLoS One · 2019
BACKGROUND: Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on l ...
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Journal ArticleClin Cancer Res · November 1, 2018
Purpose: We have shown that the aged microenvironment increases melanoma metastasis, and decreases response to targeted therapy, and here we queried response to anti-PD1.Experimental Design: We analyzed the relationship between age, response to anti-PD1, a ...
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Journal ArticleCell · October 18, 2018
Dietary soluble fibers are fermented by gut bacteria into short-chain fatty acids (SCFA), which are considered broadly health-promoting. Accordingly, consumption of such fibers ameliorates metabolic syndrome. However, incorporating soluble fiber inulin, bu ...
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Journal ArticleNature · October 2018
Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function1-4. However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian ...
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ConferenceCancer Research · July 1, 2018
AbstractAlthough the role of estrogen signaling in the progression of breast tumors and a subset of ovarian cancer patients has been underscored by the clinical use of ER antagonists, how estrogens impact th ...
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ConferenceCancer Research · July 1, 2018
AbstractIntroduction. The interruption of immune checkpoint receptor (ICR)/ligand interaction within the tumor microenvironment has become an important immunotherapy strategy. In breast cancer (BC), neither ...
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Journal ArticleJ Leukoc Biol · May 2018
Due to their cytotoxic activities, many anticancer drugs cause extensive damage to the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria that exacer ...
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Journal ArticleCell Rep · March 27, 2018
ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show that ARID1A mutati ...
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Journal ArticleNat Commun · February 12, 2018
CARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in human cancers. However, clinically applicable cancer therapeutic strategies based on CARM1 expression remain to ...
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Journal ArticleFront Immunol · 2018
Acute graft- vs. -host disease (GVHD) is an important cause of morbidity and death after allogeneic hematopoietic cell transplantation (HCT). We identify a new approach to prevent GVHD that impairs monocyte-derived dendritic cell (moDC) alloactivation of T ...
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Journal ArticleCurr Surg Rep · December 2017
PURPOSE OF REVIEW: The breast tumor microenvironment is immunosuppressive and is increasingly recognized to play a significant role in tumorigenesis. A deeper understanding of normal and aberrant interactions between malignant and immune cells has allowed ...
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Journal ArticleCancer Immunol Res · December 2017
Chimeric antigen receptors (CAR) are synthetic molecules that provide new specificities to T cells. Although successful in treatment of hematologic malignancies, CAR T cells are ineffective for solid tumors to date. We found that the cell-surface molecule ...
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Journal ArticleNat Cell Biol · August 2017
ARID1A, encoding a subunit of the SWI/SNF chromatin-remodelling complex, is the most frequently mutated epigenetic regulator across all human cancers. ARID1A and TP53 mutations are typically mutually exclusive. Therapeutic approaches that correlate with th ...
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ConferenceCancer Research · July 1, 2017
AbstractTo date there has been an increasing focus on the interactions between inflammatory myeloid cells and T cells in the tumor microenvironment because cytotoxic anti-tumoral T cells represent the chief ...
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Journal ArticleImmunity · January 17, 2017
Despite the importance of programmed cell death-1 (PD-1) in inhibiting T cell effector activity, the mechanisms regulating its expression remain poorly defined. We found that the chromatin organizer special AT-rich sequence-binding protein-1 (Satb1) restra ...
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Journal ArticleClin Cancer Res · January 15, 2017
PURPOSE: To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells. EXPERIMENTAL DESIGN: FSHR expression was determined by Western blotting, immunohistochemistry, and q ...
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Journal ArticleCancer Discov · January 2017
UNLABELLED: The role of estrogens in antitumor immunity remains poorly understood. Here, we show that estrogen signaling accelerates the progression of different estrogen-insensitive tumor models by contributing to deregulated myelopoiesis by both driving ...
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Journal ArticleTrends Cancer · January 2017
Small-molecule inhibitors offer great promise for targeting pathways that are specifically deregulated in different tumors. However, such 'targeted' therapies also elicit poorly understood effects on protective antitumor immunity. Given the emerging releva ...
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Journal ArticleCancer Res · December 1, 2016
PD-L1 antibodies produce efficacious clinical responses in diverse human cancers, but the basis for their effects remains unclear, leaving a gap in the understanding of how to rationally leverage therapeutic activity. PD-L1 is widely expressed in tumor cel ...
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Journal ArticleCancer Res · November 1, 2016
The emergence of tumor cells with certain stem-like characteristics, such as high aldehyde dehydrogenase (ALDH) activity due to ALDH1A1 expression, contributes to chemotherapy resistance and tumor relapse. However, clinically applicable inhibitors of ALDH ...
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Journal ArticleMol Cell Proteomics · November 2016
Inactivating mutations in ARID1A, which encodes a subunit of the SWI/SNF chromatin-remodeling complex, are found in over half of ovarian clear cell carcinoma cases and more broadly across most types of cancers. To identify ARID1A-dependent changes in intra ...
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Journal ArticleCancer Res · November 1, 2016
Targeted therapies elicit seemingly paradoxical and poorly understood effects on tumor immunity. Here, we show that the MEK inhibitor trametinib abrogates cytokine-driven expansion of monocytic myeloid-derived suppressor cells (mMDSC) from human or mouse m ...
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Journal ArticleOncogenesis · October 31, 2016
The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tum ...
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Journal ArticleCell Rep · September 13, 2016
Restoration of anti-tumor immunity by blocking PD-L1 signaling through the use of antibodies has proven to be beneficial in cancer therapy. Here, we show that BET bromodomain inhibition suppresses PD-L1 expression and limits tumor progression in ovarian ca ...
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Journal ArticleJ Mol Biol · August 14, 2016
Along with the discovery of tumor-driven inflammatory pathways, there has been a considerable progress over the past 10years in understanding the mechanisms leading to cancer immunosurveillance and immunoediting. Several regulatory pathways, typically invo ...
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Journal ArticlePharmacol Ther · August 2016
Dendritic cells (DCs) with robust immunosuppressive activity are commonly found in the microenvironment of advanced solid tumors. These innate immune cells are generically termed regulatory DCs and include various subsets such as plasmacytoid, conventional ...
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ConferenceCancer Research · August 1, 2016
AbstractTo date there has been an increasing focus on the interactions between inflammatory myeloid cells and T cells in the tumor microenvironment because cytotoxic anti-tumoral T cells represent the chief ...
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Journal ArticleCancer Cell · July 11, 2016
Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited ...
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Journal ArticleEur J Immunol · July 2016
In experimental autoimmune encephalomyelitis (EAE), intravenous (i.v.) injection of the antigen, myelin oligodendrocyte glycoprotein-derived peptide, MOG35-55 , suppresses disease development, a phenomenon called i.v. tolerance. Galectin-1, an endogenous g ...
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Journal ArticleCancer Res · May 1, 2016
Many signal transduction inhibitors are being developed for cancer therapy target pathways that are also important for the proper function of antitumor lymphocytes, possibly weakening their therapeutic effects. Here we show that most inhibitors targeting m ...
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Chapter · April 1, 2016
Combinatorial use of iron oxide nanoparticles (IONPs) and an alternating magnetic fi eld (AMF) can induce local hyperthermia in tumors in a controlled and uniform manner. Heating B16 primary tumors at 43°C for 30 min activated dendritic cells (DCs) and sub ...
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Journal ArticleCell Rep · February 23, 2016
Special AT-rich sequence-binding protein 1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs ...
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Journal ArticleSignal Transduct Target Ther · 2016
As tumor PD-L1 provides signals to anti-tumor PD-1+ T cells that blunt their functions, αPD-1 and αPD-L1 antibodies have been developed as anti-cancer immunotherapies based on interrupting this signaling axis. However, tumor cell-intrinsic PD-L1 signals al ...
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ConferenceCancer Immunology Research · January 1, 2016
AbstractHumans are symbiotic organisms in which bacteria outnumber eukaryotic cells in a ratio of 10 to 1. Interactions between commensal microorganisms and immune cells at mucosal surfaces forge the orchest ...
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Journal ArticleImmunity · December 15, 2015
Commensal microorganisms influence malignant progression by altering systemic inflammation. New data from two groups (Vétizou et al., 2015; Sivan et al., 2015) indicate that the abundance of specific commensal bacterial species enhances the anti-cancer act ...
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Journal ArticleProc Natl Acad Sci U S A · November 17, 2015
Telomeric repeat-containing RNA (TERRA) has been identified as a telomere-associated regulator of chromosome end protection. Here, we report that TERRA can also be found in extracellular fractions that stimulate innate immune signaling. We identified extra ...
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Journal ArticleOpen Life Sci · October 2015
The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates many important cellular functions. The functional impact of deregulating the PIK3CA gene, encoding the p110α catalytic subunit of PI3K, is validated by frequent gain of function mutations ...
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ConferenceCancer Immunology Research · October 1, 2015
AbstractTumor-recruited myeloid cells represent a significant portion of inflammatory cells within the tumor microenvironment and influence nearly all steps of tumor progression. Although tumor-associated ne ...
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Journal ArticleVaccine · August 20, 2015
Identifying new molecular adjuvants that elicit effective vaccine-induced CD8(+) T cell immunity may be critical for the elimination of many challenging diseases including Tuberculosis, HIV and cancer. Here, we report that co-administration of molecular ad ...
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Journal ArticleOncoimmunology · August 2015
We have reported that TLR5-mediated recognition of commensal microbiota modulates systemic tumor-promoting inflammation and malignant progression of tumors at distal locations. Approximately 7-10% of the general population harbors a deleterious single nucl ...
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Journal ArticleCell · June 18, 2015
Dendritic cells (DCs) are required to initiate and sustain T cell-dependent anti-cancer immunity. However, tumors often evade immune control by crippling normal DC function. The endoplasmic reticulum (ER) stress response factor XBP1 promotes intrinsic tumo ...
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Journal ArticleNat Med · March 2015
The gene encoding ARID1A, a chromatin remodeler, shows one of the highest mutation rates across many cancer types. Notably, ARID1A is mutated in over 50% of ovarian clear cell carcinomas, which currently have no effective therapy. To date, clinically appli ...
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Journal ArticleCancer Cell · January 12, 2015
The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-d ...
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Journal ArticleOncoscience · 2015
Recent studies have demonstrated that the commensal microbiota are indispensable for the maintenance of immune homeostasis, orchestration of immune responses against pathogens and most recently during cancer immunotherapy and malignant progression of extra ...
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Chapter · 2015
During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota re ...
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Journal ArticleJ Clin Invest · December 2014
Infiltrating inflammatory cells are highly prevalent within the tumor microenvironment and mediate many processes associated with tumor progression; however, the contribution of specific populations remains unclear. For example, the nature and function of ...
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Journal ArticleBreast Cancer Res Treat · October 2014
Mesothelin is a potential therapeutic target and prognostic marker in breast cancer. However, results on its prognostic value in breast cancer have been equivocal and warranted further evaluation. We analyzed clinical data from two breast cancer patient co ...
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Journal ArticleImmunity · September 18, 2014
Tumor-reactive T cells become unresponsive in advanced tumors. Here we have characterized a common mechanism of T cell unresponsiveness in cancer driven by the upregulation of the transcription factor Forkhead box protein P1 (Foxp1), which prevents CD8⁺ T ...
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Journal ArticleNanomedicine · August 2014
UNLABELLED: Combinatorial use of iron oxide nanoparticles (IONPs) and an alternating magnetic field (AMF) can induce local hyperthermia in tumors in a controlled and uniform manner. Heating B16 primary tumors at 43°C for 30 min activated dendritic cells (D ...
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Journal ArticleJ Vis Exp · March 26, 2014
Breast cancer is a heterogeneous disease involving complex cellular interactions between the developing tumor and immune system, eventually resulting in exponential tumor growth and metastasis to distal tissues and the collapse of anti-tumor immunity. Many ...
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Journal ArticleJ Cell Physiol · January 2014
Although recent evidence indicates that several chemokines and defensins, well-known as inflammatory mediators, are expressed in the male and female reproductive tracts, the location and functional significance of chemokine networks in sperm physiology and ...
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Journal ArticleFront Immunol · December 10, 2013
A common characteristic of solid tumors is the pathological recruitment of immunosuppressive myeloid cells, which in certain tumors includes dendritic cells (DCs). DCs are of particular interest in the field of cancer immunotherapy because they induce pote ...
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Journal ArticleHum Pathol · November 2013
Fibroblast activation protein (FAP) has long been known to be expressed in the stroma of breast cancer. However, very little is known if the magnitude of FAP expression within the stroma may have a prognostic value and reflect the heterogeneous biology of ...
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Journal ArticleCancer Res · July 1, 2013
Reversing tumor-associated immunosuppression seems necessary to stimulate effective therapeutic immunity against lethal epithelial tumors. Here, we show this goal can be addressed using cps, an avirulent, nonreplicating uracil auxotroph strain of the paras ...
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Journal ArticleCell Cycle · July 1, 2013
Inhibitors of EZH2 methyltransferase activity have been demonstrated to selectively suppress the growth of diffused large B cell lymphoma (DLBCL) cells with gain-of-function mutations in EZH2, while exhibiting very limited effects on the growth of DLBCL ce ...
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Journal ArticleMicrorna Diagn Ther · April 26, 2013
It is becoming increasingly clear that there are unique sets of miRNAs that have distinct governing roles in several aspects of both innate and adaptive immune responses. In addition, new tools allow selective modulation of the expression of individual miR ...
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Journal ArticleIntegr Biol (Camb) · January 2013
Nanotechnology has great potential to produce novel therapeutic strategies that target malignant cells through the ability of nanoparticles to get access to and be ingested by living cells. However its specificity for accumulation in tumors, which is the k ...
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Journal ArticleCancer Immunol Immunother · December 2012
Mast cells have emerged as critical intermediaries in the regulation of peripheral tolerance. Their presence in many precancerous lesions and tumors is associated with a poor prognosis, suggesting mast cells may promote an immunosuppressive tumor microenvi ...
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Journal ArticleAm J Physiol Lung Cell Mol Physiol · September 15, 2012
In the clinical setting, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene enhance the inflammatory response in the lung to Pseudomonas aeruginosa (P. aeruginosa) infection. However, studies on human airway epithelial cells i ...
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Journal ArticleJ Cell Sci · September 15, 2012
Telomeres play crucial roles in the maintenance of genome integrity and control of cellular senescence. Most eukaryotic telomeres can be transcribed to generate a telomeric repeat-containing RNA (TERRA) that persists as a heterogeneous nuclear RNA and can ...
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Journal ArticleOncoimmunology · September 1, 2012
Current ovarian cancer treatments based on surgery/chemotherapy show limited efficacy. Targeting immunosuppression is a requirement for the effectiveness of novel promising anti-tumor immunotherapies. Our latest work in preclinical models shows that nanopa ...
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Journal ArticleExpert Rev Obstet Gynecol · September 1, 2012
After more than 30 years of iterations of surgical debulking plus chemotherapy, the need for complementary ovarian cancer treatments has become clear. In the ovarian cancer microenvironment, myeloid immunosuppressive leukocytes, lymphocytes, fibroblasts an ...
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Journal ArticleBreast Cancer Res Treat · June 2012
Mesothelin is a cell-surface glycoprotein present on mesothelial cells and elicits T cell responses in a variety of cancers including pancreatic, biliary and ovarian cancer. Breast cancer is not known to express mesothelin. We postulated that mesothelin ma ...
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Journal ArticleCancer Res · April 1, 2012
Modulating the activity of miRNAs provides opportunities for novel cancer interventions. However, low bioavailability and poor cellular uptake are major challenges for delivering miRNA mimetics specifically to tumor cells. Here, we took advantage of the sp ...
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Journal ArticleJ Exp Med · March 12, 2012
We characterized the initiation and evolution of the immune response against a new inducible p53-dependent model of aggressive ovarian carcinoma that recapitulates the leukocyte infiltrates and cytokine milieu of advanced human tumors. Unlike other models ...
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Journal ArticleOncotarget · March 2012
In conclusion, our work expands our understanding of tumor progression and provides further mechanistic rationale to develop novel interventions targeting immunosuppression. Future studies should unveil other unrecognized aspects of the contribution of the ...
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Journal ArticleCell Immunol · 2012
The immune surveillance hypothesis proposed over 50 years ago that many precancerous lesions are eliminated without a histological trace due to immunological pressure. Since then, it has become apparent that both the tumor and the anti-cancer immune respon ...
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Chapter · 2012
The lack of targeted therapy for women with triple negative breast cancer demands a "think-outside-the-box" approach in search of novel treatment strategies. Although cancer drug development traditionally focused on targeting the tumor cell cycle, emphasis ...
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Journal ArticleOncotarget · September 2010
CD277, a member of the butyrophilin subfamily 3 (BTN3), shares significant sequence similarities and predicted common structural features with inhibitory B7-H4 and other members of the B7 superfamily. Here we report that CD277 is consistently expressed in ...
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Journal ArticleClin Cancer Res · August 15, 2010
PURPOSE: High-throughput profiling experiments have linked altered expression of microRNAs (miRNA) to different types of cancer. Tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment ele ...
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Journal ArticleJ Immunol · May 15, 2010
T cell adoptive transfer strategies that have produced clinical remissions against specific tumors have so far produced disappointing results against ovarian cancer. Recent evidence suggests that adoptively transferred CD4(+) T cells can trigger endogenous ...
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ConferenceCancer Research · April 15, 2010
AbstractMicroRNAs (miRNAs) are a class of short non-coding regulatory RNA genes, which have been implicated in the control of developmental, physiological and pathological processes. High-throughput profilin ...
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Journal ArticleJ Exp Med · March 15, 2010
RNA splicing is an increasingly recognized regulator of immunity. Here, we demonstrate that after Mycobacterium tuberculosis infection (mRNA) il12rb1 is spliced by dendritic cells (DCs) to form an alternative (mRNA) il12rb1Deltatm that encodes the protein ...
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Journal ArticleCell Cycle · January 15, 2010
Current therapies for metastatic ovarian carcinoma are based on surgical debulking followed by chemotherapy. After more than three decades implementing treatments that selectively target the tumor cell, the 5-year survival rate for metastatic ovarian cance ...
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Journal ArticleClin Dev Immunol · 2010
Adoptive T cell transfer therapy, the ex vivo activation, expansion, and subsequent administration of tumor-reactive T cells, is already the most effective therapy against certain types of cancer. However, recent evidence in animal models and clinical tria ...
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Journal ArticleCancer Res · September 15, 2009
Boosting therapeutically relevant immunity against lethal epithelial tumors may require targeting tumor-induced immunosuppression on an individualized basis. Here, we show that, in the ovarian carcinoma microenvironment, CD11c(+)MHC-II(+) dendritic cells s ...
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Journal ArticleJ Clin Invest · August 2009
The success of clinically relevant immunotherapies requires reversing tumor-induced immunosuppression. Here we demonstrated that linear polyethylenimine-based (PEI-based) nanoparticles encapsulating siRNA were preferentially and avidly engulfed by regulato ...
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Journal ArticleCancer Res · August 1, 2009
Adoptive transfer of antitumor T cells is a promisingly effective therapy for various cancers, but its effect on endogenous antitumor immune mechanisms remains largely unknown. Here, we show that the administration of naive T cells de novo primed for only ...
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Journal ArticleJ Transl Med · June 19, 2009
BACKGROUND: Murine studies suggest that myeloid cells such as vascular leukocytes (VLC) and Tie2+ monocytes play a critical role in tumor angiogenesis and vasculogenesis. Myeloid cells are a primary cause of resistance to anti-VEGF therapy. The elimination ...
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Journal ArticleAm J Reprod Immunol · January 2009
PROBLEM: The initiation of an immune response often involves the cooperation of various innate immune cells. In the human endometrium, uterine natural killer (uNK) cells and uterine macrophages are present in significant numbers and in close proximity, yet ...
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Journal ArticleClin Immunol · November 2008
The human endometrium undergoes cyclical changes regulated by sex hormones. Evidence suggests that sex hormones regulate NK cell recruitment into the uterus in large numbers. NKG2D is an activating receptor expressed on human NK cells, gammadelta and CD8 T ...
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Journal ArticleCancer Res · September 15, 2008
Dendritic cells (DC) and cytokines that expand myeloid progenitors are widely used to treat cancer. Here, we show that CD11c(+)DEC205(+) DCs coexpressing alpha-smooth muscle actin and VE-cadherin home to perivascular areas in the ovarian cancer microenviro ...
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Journal ArticleBlood · August 15, 2008
Robust T-cell responses without autoimmunity are only possible through a fine balance between activating and inhibitory signals. We have identified a novel modulator of T-cell expansion named proliferation-induced lymphocyte-associated receptor (PILAR). Su ...
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Chapter · 2008
Vascular leukocytes are a unique population of CD45+ VE-cadherin+ cells with diverse functions. VLCs are capable of antigen presentation, as well as formation of endothelial-like structures in vitro and in vivo. VLCs are largely present among CD45+ cells i ...
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Journal ArticleCancer Res · May 15, 2007
Despite advancements in the treatment of ovarian cancer, this disease continues to be a leading cause of cancer death in women. Adoptive transfer of tumor-reactive T cells is a promising antitumor therapy for many cancers. We designed a chimeric receptor l ...
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Journal ArticleCancer Res · May 15, 2007
Immunosuppressive leukocytes are emerging as a critical factor in facilitating tumor progression. These leukocytes are converted by the tumor microenvironment to become tolerogenic, facilitate metastasis, and to aid in neovascularization. The predominant v ...
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Chapter · January 1, 2007
Emerging evidence over the past decade has revealed the significance of tumor-host interactions and of the tumor microenvironment in tumor growth and progression. Among these mechanisms, a bulk of experimental evidence in animal tumor models has clearly es ...
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Journal ArticleCancer Biol Ther · July 2006
We tested whether tumor cells were killed by replication-incompetent recombinant herpes simplex virus (HSV) d120 lacking immediate early gene ICP4 and whether HSVd120-killed tumor cells could be used directly for tumor vaccination. Vaccine efficacy was tes ...
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Journal ArticleCancer Biol Ther · June 2006
Expression profiling using microarrays has become an essential tool for interrogating tumor biology. However, profiling of whole tumor RNA reflects both tumor and host cells, making it difficult to dissect molecular events within specific cellular compartm ...
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Journal ArticleCancer Gene Ther · February 2006
The use of dendritic cells (DCs) loaded with apoptotic tumor cells is an attractive approach to tumor vaccination in the absence of well-characterized tumor antigens. Apoptotic tumor cells are a convenient source of polyvalent tumor antigen, but may induce ...
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Journal ArticleMol Ther · November 2005
Cooperation between oncolytic herpes simplex virus (HSV) and host effector immune mechanisms has been previously described. In the present study, we investigated the mechanism underlying such cooperation in a murine syngeneic model of ovarian carcinoma. Th ...
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Journal ArticleExpert Opin Biol Ther · September 2005
Gynaecological malignancies, excluding breast cancer, cause approximately 25,000 deaths yearly among women in the US. Therefore, novel approaches for the prevention or treatment of these diseases are urgently required. In the case of cervical cancer, human ...
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Journal ArticleHum Gene Ther · June 2005
In the present study, we investigated the ability of replication-restricted herpes simplex virus (HSV) 1716 lacking ICP34.5 to infect endothelium and disrupt tumor vasculature. HSV-1716 efficiently infected and killed mouse endothelial cell lines H5V and M ...
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Journal ArticleBr J Cancer · April 11, 2005
In this review, we discuss the recent identification in vivo of a population of CD11c+ cells exhibiting simultaneous expression of both endothelial and dendritic cell markers, termed vascular leukocytes (VLCs). VLCs are highly represented in human ovarian ...
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Journal ArticleBlood · January 15, 2005
There is no proof that hematopoietic cells contribute significantly to vasculogenesis in postnatal life. Here we report a novel leukocyte subset within ovarian carcinoma that coexpresses endothelial and dendritic cell markers. Fluorescence-activated cell s ...
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Journal ArticleNat Med · September 2004
The involvement of immune mechanisms in tumor angiogenesis is unclear. Here we describe a new mechanism of tumor vasculogenesis mediated by dendritic cell (DC) precursors through the cooperation of beta-defensins and vascular endothelial growth factor-A (V ...
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Journal ArticleNat Med · September 2004
Regulatory T (T(reg)) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by T(reg) cells; ...
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Journal ArticleCancer Res · March 15, 2004
The role of the NKG2D immunoreceptor and its ligands in antitumor immune response is incompletely understood. Here, we report that effector immune cells infiltrating ovarian carcinoma are mostly CD8+ lymphocytes lacking CD28 but expressing the NKG2D costim ...
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Journal ArticleToxicology · July 15, 2003
The immunosuppressive drug cyclosporine A (CsA) has been successfully used in several diseases with immunological basis and in transplant patients. Nephrotoxicity is the main secondary effect of CsA treatment. Although the mechanisms of nephrotoxitity are ...
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Journal ArticleGenomics · February 2003
Human beta-defensins are a family of cationic peptides that share a pattern of six conserved cysteine residues. We describe the cloning and characterization of the cDNAs of five novel beta-defensin genes (DEFB25-DEFB29) clustered on chromosome 20p13, which ...
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Journal ArticleN Engl J Med · January 16, 2003
BACKGROUND: Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established. METHODS: We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ov ...
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Journal ArticleCancer Biol Ther · 2003
NKG2D serves as one of the most potent activating receptors for effector lymphocytes. in peripheral tissues. Here we report the characterization of Letal, the first human trans-membrane NKG2D ligand lacking an immunoglobulin-like alpha-3 ectodomain. Letal ...
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Journal ArticleProtein Sci · January 2003
The human genome contains numerous genes whose protein products are unknown in terms of structure, interaction partner, expression, and function. To unravel the function of these orphan genes, it is of particular value to isolate native forms of protein an ...
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Journal ArticleClin Cancer Res · January 2003
The first tissue-specific angiogenic molecule, endocrine gland-derived vascular endothelial growth factor (EG-VEGF), was identified recently in human ovary, raising hopes of developing tumor type-specific angiogenesis inhibitors. In the present study, we a ...
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Journal ArticleBiochem Biophys Res Commun · April 12, 2002
Vascular endothelial growth factor (VEGF) has been implicated as a potent regulator of angiogenesis in tumors, and its protein exists as at least five isoforms with distinct biologic activities and clinical significance. Tumors under metabolic stress condi ...
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Journal ArticleProtein Sci · December 2001
Defensins are cationic and cysteine-rich peptides that play a crucial role in the host defense against microorganisms of many organisms by their capability to permeabilize bacterial membranes. The low sequence similarity among the members of the large mamm ...
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Journal ArticleCell Tissue Res · November 2001
Previous studies have shown the implication of beta-defensins in host defense of the human body. The human beta-defensins 1 and 2 (hBD-1, hBD-2) have been isolated by biochemical methods. Here we report the identification of a third human beta-defensin, ca ...
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Journal ArticlePancreas · May 2001
The presence of telomerase activity has been proposed as a specific and sensitive marker for malignant tissue, and positivity rates of up to 95% have been reported in pancreatic cancer. In the present study telomerase activity analysis was reevaluated in 2 ...
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Journal ArticlePain · April 2001
Recent theories of pathogenesis of pain in chronic pancreatitis (CP) are neuroimmune interactions of intrapancreatic nerves and inflammatory cells and increase in levels of pain neurotransmitters such as substance P (SP). This study analyzed the expression ...
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Journal ArticleSurgery · November 2000
BACKGROUND: The immunologic mechanisms involved in the development of chronic pancreatitis (CP) are poorly understood. Chronically inflamed tissues contain increased numbers of mononuclear cells expressing the CC chemokine receptor 5 (CCR5), which is also ...
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Journal ArticleInt J Cancer · October 1, 2000
Syndecan-1 belongs to the syndecan family of cell surface transmembrane heparan-sulfate proteoglycans, which participate in cell proliferation, cell migration and cell-matrix interactions. Decreased expression of syndecan-1 has been observed in some gastro ...
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Journal ArticleTransplantation · November 27, 1998
BACKGROUND: We report an investigation of the effects of cyclosporine (CsA) on kidney function, the glomerular synthesis of reactive oxygen species, the peroxidation of lipids, and the levels of thromboxane B2 (TXB2). The effect of the simultaneous adminis ...
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Journal ArticleEur J Clin Chem Clin Biochem · February 1996
In order to discriminate between malignant and benign effusions, the values of tissue polypeptide specific antigen,carcinoembryonic antigen and squamous cell carcinoma associated antigen were measured in the pleural fluid of 30 patients with neoplasm, 10 w ...
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Journal ArticleScand J Clin Lab Invest · December 1995
Zone electrophoresis of serum proteins is still widely performed as a routine procedure in clinical laboratories. It is used in the diagnosis and management of many disorders, e.g. monoclonal gammopathies, cirrhosis, nephrotic syndrome, acute-phase reactio ...
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