Scholars@Duke
Brent A. Hanks

Brent A. Hanks

Associate Professor of Medicine
Medicine, Medical Oncology
hanks004@mc.duke.edu
LSRC, Box 91004, Pharmacology and Cancer Biology, Durham, NC 27708
308 Research Drive, LSRC, Room C162, Durham, NC 27708
Office hours

Selected Publications

Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma.

Journal Article J Gastrointest Cancer · June 2024 BACKGROUND: Gastroesophageal cancer is a major cause of cancer-related mortality worldwide. Treatment of both early stage and advanced disease remains highly reliant on cytotoxic chemotherapy. About 4-24% of gastroesophageal cancers are microsatellite inst ... Full text Link to item Cite

A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression.

Journal Article Sci Immunol · May 10, 2024 Conventional dendritic cells (DCs) are essential mediators of antitumor immunity. As a result, cancers have developed poorly understood mechanisms to render DCs dysfunctional within the tumor microenvironment (TME). After identification of CD63 as a specif ... Full text Link to item Cite

Gli2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating Wnt Ligand and Prostaglandin Signaling.

Journal Article bioRxiv · April 1, 2024 UNLABELLED: Therapeutic resistance to immune checkpoint blockade has been commonly linked to the process of mesenchymal transformation (MT) and remains a prevalent obstacle across many cancer types. An improved mechanistic understanding for MT-mediated imm ... Full text Link to item Cite

Assessing the utility of molecular diagnostic classification for cancers of unknown primary.

Journal Article Cancer Med · October 2023 BACKGROUND: Roughly 5% of metastatic cancers present with uncertain origin, for which molecular classification could influence subsequent management; however, prior studies of molecular diagnostic classifiers have reported mixed results with regard to clin ... Full text Link to item Cite

Multicenter Experience with Neoadjuvant Therapy in Melanoma Highlights Heterogeneity in Contemporary Practice.

Journal Article Ann Surg · June 1, 2023 OBJECTIVE: To determine the feasibility and impact of neoadjuvant therapy (NT) in patients who present with advanced melanoma amenable to surgical resection. SUMMARY BACKGROUND DATA: Given current effective systemic therapy for melanoma, the use of NT is b ... Full text Link to item Cite

The Enduring Effects of COVID for Cancer Care: Learning from Real-Life Clinical Practice.

Journal Article Clin Cancer Res · May 1, 2023 For three years, COVID-19 has circulated among our communities and around the world, fundamentally changing social interactions, health care systems, and service delivery. For people living with (and receiving treatment for) cancer, pandemic conditions pre ... Full text Link to item Cite

Data from APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell–Mediated Antitumor Immune Responses

Other · April 4, 2023 <div>Abstract<p>The APOBEC family of cytidine deaminases is one of the most common endogenous sources of mutations in human cancer. Genomic studies of tumors have found that APOBEC mutational signatures are enriched in the HER2 subtype ... Full text Cite

Data from APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell–Mediated Antitumor Immune Responses

Other · April 4, 2023 <div>Abstract<p>The APOBEC family of cytidine deaminases is one of the most common endogenous sources of mutations in human cancer. Genomic studies of tumors have found that APOBEC mutational signatures are enriched in the HER2 subtype ... Full text Cite

Abstract 2892: A SREBF2-dependent genetic program drives a novel immunotolerant dendritic cell population that supports cancer progression

Journal Article Cancer Research · April 4, 2023 AbstractThe development of immune responses to cancers are crucially dependent upon effective antigen cross-presentation by local dendritic cell (DC) populations. Indeed, DC-mediated T cell stimulation is es ... Full text Cite

Supplementary Figure S6 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>Select gene expression changes following anti-PD1 escape based on RNAseq transcriptional analysis.</p> ... Full text Cite

Supplementary Figure S3 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>Effect of TGFbeta blockade on FSP IHC in the BRAF-PTEN melanoma model.</p> ... Full text Cite

Supplementary Figure S3 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>Effect of TGFbeta blockade on FSP IHC in the BRAF-PTEN melanoma model.</p> ... Full text Cite

Supplementary Figure S4 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>BRAF-PTEN/MAF cell line validation by Western blot. Impact of MAFs on melanoma gene expression based on qrt-PCR. TGFbeta blockade effect on TBR1 and TBRII gene expression based on qrt-PCR.</p> ... Full text Cite

Supplementary Figure S5 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>Effect of melanoma-associated fibroblast MMP9 on immune responses to anti-PD1 therapy.</p> ... Full text Cite

Supplementary Figure S5 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>Effect of melanoma-associated fibroblast MMP9 on immune responses to anti-PD1 therapy.</p> ... Full text Cite

Data from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <div>Abstract<p>Although anti–PD-1 therapy has improved clinical outcomes for select patients with advanced cancer, many patients exhibit either primary or adaptive resistance to checkpoint inhibitor immunotherapy. The role of the tumor ... Full text Cite

Supplementary Figure S6 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>Select gene expression changes following anti-PD1 escape based on RNAseq transcriptional analysis.</p> ... Full text Cite

Supplementary Figure S1 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>TGFbeta inhibition augments the efficacy of anti-CTLA-4 antibody immunotherapy.</p> ... Full text Cite

Supplementary Figure S4 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>BRAF-PTEN/MAF cell line validation by Western blot. Impact of MAFs on melanoma gene expression based on qrt-PCR. TGFbeta blockade effect on TBR1 and TBRII gene expression based on qrt-PCR.</p> ... Full text Cite

Supplementary Figure S1 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <p>TGFbeta inhibition augments the efficacy of anti-CTLA-4 antibody immunotherapy.</p> ... Full text Cite

Data from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

Other · April 3, 2023 <div>Abstract<p>Although anti–PD-1 therapy has improved clinical outcomes for select patients with advanced cancer, many patients exhibit either primary or adaptive resistance to checkpoint inhibitor immunotherapy. The role of the tumor ... Full text Cite

Data from Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma

Other · March 31, 2023 <div>AbstractPurpose:<p>In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanom ... Full text Cite

Data from Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma

Other · March 31, 2023 <div>AbstractPurpose:<p>In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanom ... Full text Cite

Tumor-intrinsic NLRP3-HSP70-TLR4 axis drives premetastatic niche development and hyperprogression during anti-PD-1 immunotherapy.

Journal Article Sci Transl Med · November 23, 2022 The tumor-intrinsic NOD-, LRR- and pyrin domain-containing protein-3 (NLRP3) inflammasome-heat shock protein 70 (HSP70) signaling axis is triggered by CD8+ T cell cytotoxicity and contributes to the development of adaptive resistance to anti-programmed cel ... Full text Link to item Cite

513 Overcoming hedgehog mediated anti-PD-1 resistance in melanoma through prostaglandin inhibition

Conference Regular and Young Investigator Award Abstracts · November 2022 Full text Cite

Identification of a Germline Pyrin Variant in a Metastatic Melanoma Patient With Multiple Spontaneous Regressions and Immune-related Adverse Events.

Journal Article J Immunother · July 2022 The mechanisms underlying tumor immunosurveillance and their association with the immune-related adverse events (irAEs) associated with checkpoint inhibitor immunotherapies remain poorly understood. We describe a metastatic melanoma patient exhibiting mult ... Full text Open Access Link to item Cite

The "Inside" Story on Tumor-Expressed PD-L1.

Journal Article Cancer Res · June 6, 2022 While the extracellular domain of PD-L1 is well-recognized for playing a critical role in immune evasion by suppressing CD8+ T-cell activity through direct PD-1 interactions, a series of studies has evolved highlighting important functional roles for the P ... Full text Link to item Cite

Clinical Trials with Biologic Primary Endpoints in Immuno-oncology: Concepts and Usage.

Journal Article Clin Cancer Res · January 1, 2022 Clinical trials that have a pharmacokinetic or a pharmacodynamic immunologic mechanism of action-based primary outcome could substantially improve the validity and efficiency of early development of immuno-oncology agents. Here, we outline different trial ... Full text Link to item Cite

APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell-Mediated Antitumor Immune Responses.

Journal Article Cancer Immunol Res · January 2022 The APOBEC family of cytidine deaminases is one of the most common endogenous sources of mutations in human cancer. Genomic studies of tumors have found that APOBEC mutational signatures are enriched in the HER2 subtype of breast cancer and are associated ... Full text Link to item Cite

Inhibition of estrogen signaling in myeloid cells increases tumor immunity in melanoma.

Journal Article J Clin Invest · December 1, 2021 Immune checkpoint blockade (ICB) therapies have significantly prolonged patient survival across multiple tumor types, particularly in melanoma. Interestingly, sex-specific differences in response to ICB have been observed, with males receiving a greater be ... Full text Open Access Link to item Cite

319 The tumor-intrinsic NLRP3 inflammasome establishes a pulmonary metastatic niche via type II epithelial HSP70/TLR4 signaling and facilitates disease hyperprogression in response to immunotherapy

Conference Journal for ImmunoTherapy of Cancer · November 2021 BackgroundOur understanding of those underlying mechanisms that contribute to metastatic progression in melanoma remains limited. While uncommon, melanoma hyperprogression in response to immunotherapy is likely to ... Full text Cite

Overcoming Immunotherapy Resistance by Targeting the Tumor-Intrinsic NLRP3-HSP70 Signaling Axis.

Journal Article Cancers (Basel) · September 23, 2021 The tumor-intrinsic NOD-like receptor family, pyrin-domain-containing-3 (NLRP3) inflammasome, plays an important role in regulating immunosuppressive myeloid cell populations in the tumor microenvironment (TME). While prior studies have described the activ ... Full text Open Access Link to item Cite

An immunogenomic analysis of melanoma brain metastases (MBM) compared to extracranial metastases (ECM).

Conference Journal of Clinical Oncology · May 20, 2021 9521 Background: Previous work has shown that MBM have a unique molecular profile compared to ECM. Description of the biology of MBM will facilitate the design of rational therapies for patients (pts) with MBM. Methods: We analyz ... Full text Cite

The State of Melanoma: Emergent Challenges and Opportunities.

Journal Article Clin Cancer Res · May 15, 2021 Five years ago, the Melanoma Research Foundation (MRF) conducted an assessment of the challenges and opportunities facing the melanoma research community and patients with melanoma. Since then, remarkable progress has been made on both the basic and clinic ... Full text Link to item Cite

Pharmacological Wnt ligand inhibition overcomes key tumor-mediated resistance pathways to anti-PD-1 immunotherapy.

Journal Article Cell reports · May 2021 While immune checkpoint blockade is associated with prolonged responses in multiple cancers, most patients still do not benefit from this therapeutic strategy. The Wnt-β-catenin pathway is associated with diminished T cell infiltration; however, activating ... Full text Open Access Cite

Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma.

Journal Article J Immunother Cancer · April 2021 BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study wa ... Full text Open Access Link to item Cite

Ipilimumab and Radiation in Patients with High-risk Resected or Regionally Advanced Melanoma.

Journal Article Clin Cancer Res · March 1, 2021 PURPOSE: In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma. PATIENTS AND METHODS: Twenty-fou ... Full text Link to item Cite

Tumor Mutational Burden as a Predictor of Immunotherapy Response: Is More Always Better?

Journal Article Clin Cancer Res · March 1, 2021 Immune checkpoint inhibitors, including antibodies that block programmed cell death protein-1 (PD-1) and PD-L1, have transformed the management of many cancers. However, the majority of patients have primary or acquired resistance to these immunotherapies. ... Full text Link to item Cite

Dissecting the immune landscape of tumor draining lymph nodes in melanoma with high-plex spatially resolved protein detection.

Journal Article Cancer Immunol Immunother · February 2021 BACKGROUND: In melanoma patients, microscopic tumor in the sentinel lymph-node biopsy (SLN) increases the risk of distant metastases, but the transition from tumor in the SLN to metastatic disease remains poorly understood. METHODS: Fluorescent staining fo ... Full text Link to item Cite

A case report of microsatellite instability (MSI)-high, HER2 amplified pancreatic adenocarcinoma with central nervous system metastasis.

Journal Article AME case reports · January 2021 Pancreatic adenocarcinoma commonly presents as metastatic disease and harbors a dire prognosis due to its aggressive behavior, propensity for resistance to therapies, and lack of targetable driver mutations. Additionally, despite advances in other cancers, ... Full text Cite

The utility of initial staging PET-CT as a baseline scan for surveillance imaging in stage II and III melanoma.

Journal Article Surg Oncol · December 2020 BACKGROUND: This study evaluates the utility of whole-body PET-CT for the initial staging and subsequent surveillance imaging of patients with completely resected stage II and stage III melanoma. METHODS: A single-center, retrospective review of patients w ... Full text Link to item Cite

Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets.

Journal Article Nat Cancer · December 2020 Generating responses to tumor antigens poses a challenge for immunotherapy. This phase II trial (NCT02129075) tested fms-like tyrosine kinase 3 (Flt3) ligand pre-treatment enhancement of responses to dendritic cell (DC)-targeting vaccines. We evaluated a r ... Full text Link to item Cite

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery.

Journal Article J Immunother Cancer · December 2020 Since the publication of the Society for Immunotherapy of Cancer's (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune che ... Full text Open Access Link to item Cite

Higher BMI, But Not Sarcopenia, Is Associated With Pembrolizumab-related Toxicity in Patients With Advanced Melanoma.

Journal Article Anticancer Res · September 2020 BACKGROUND/AIM: To determine whether BMI and sarcopenia were related to treatment-limiting toxicity or efficacy of pembrolizumab treatment in melanoma patients. PATIENTS AND METHODS: Medical records for melanoma patients undergoing pembrolizumab treatment ... Full text Link to item Cite

Role of dendritic cell metabolic reprogramming in tumor immune evasion.

Journal Article International immunology · June 2020 The dendritic cell (DC) is recognized as a vital mediator of anti-tumor immunity. More recent studies have also demonstrated the important role of DCs in the generation of effective responses to checkpoint inhibitor immunotherapy. Metabolic programming of ... Full text Cite

A tumor-intrinsic PD-L1/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy.

Journal Article J Clin Invest · May 1, 2020 An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several p ... Full text Link to item Cite

Retrospective analysis of safety and efficacy of anti-PD-1 therapy and radiation therapy in advanced melanoma: A bi-institutional study.

Journal Article Radiother Oncol · September 2019 BACKGROUND AND PURPOSE: Antibodies against programmed cell death protein 1 (PD-1) are standard treatments for advanced melanoma. Palliative radiation therapy (RT) is commonly administered for this disease. Safety and optimal timing for this combination for ... Full text Link to item Cite

Blood-based genomic profiling of cell-free DNA (cfDNA) to identify microsatellite instability (MSI-H), tumor mutational burden (TMB) and Wnt/B-Catenin pathway alterations in patients with gastrointestinal (GI) tract cancers.

Conference Journal of Clinical Oncology · May 20, 2019 3552 Background: MSI-H cancers are responsive to immune checkpoint blockade (ICB), but nearly half of all patients experience primary or early treatment resistance. Activation of the WNT/B-Catenin pathway can lead to immune exclu ... Full text Cite

The Emerging Role of Surgery for Patients With Advanced Melanoma Treated With Immunotherapy.

Journal Article J Surg Res · April 2019 BACKGROUND: The emergence of immune checkpoint inhibitors (ICIs) has improved survival for patients with metastatic melanoma. The types of disease-response patterns to ICI therapy can be more complex relative to traditional chemotherapy and include mixed r ... Full text Link to item Cite

Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.

Journal Article J Clin Oncol · March 20, 2019 PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) comp ... Full text Link to item Cite

Phase 1/2 study of epacadostat in combination with ipilimumab in patients with unresectable or metastatic melanoma.

Journal Article J Immunother Cancer · March 20, 2019 BACKGROUND: Epacadostat is a potent inhibitor of the immunosuppressive indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. We present phase 1 results from a phase 1/2 clinical study of epacadostat in combination with ipilimumab, an anti-cytotoxic T-lymphocyte-ass ... Full text Open Access Link to item Cite

Updates in adjuvant systemic therapy for melanoma.

Journal Article J Surg Oncol · January 2019 There has been a rapid increase in adjuvant therapies approved for treatment following surgical resection of stages III/IV melanoma. We review current indications for adjuvant therapy, which currently includes a heterogenous group of stages III and IV pati ... Full text Link to item Cite

Role of Tumor-Mediated Dendritic Cell Tolerization in Immune Evasion.

Journal Article Front Immunol · 2019 The vast majority of cancer-related deaths are due to metastasis, a process that requires evasion of the host immune system. In addition, a significant percentage of cancer patients do not benefit from our current immunotherapy arsenal due to either primar ... Full text Open Access Link to item Cite

Stromal Fibroblasts Mediate Anti-PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma.

Journal Article Cancer Immunol Res · December 2018 Although anti-PD-1 therapy has improved clinical outcomes for select patients with advanced cancer, many patients exhibit either primary or adaptive resistance to checkpoint inhibitor immunotherapy. The role of the tumor stroma in the development of these ... Full text Open Access Link to item Cite

Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization.

Journal Article Immunity · January 16, 2018 Featured Publication Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have des ... Full text Open Access Link to item Cite

Immune Checkpoint Combinations with Inflammatory Pathway Modulators

Chapter · January 1, 2018 Immune checkpoint inhibition of program death protein-1 (PD-1) and its ligands PD-L1 and PD-L2 is an established therapeutic modality in melanoma, non-small cell lung cancer, renal cell carcinoma, and other tumor types. Unfortunately, 60 to 80% of all pati ... Full text Cite

Paracrine wnt-β-catenin signaling inhibition as a strategy to enhance the efficacy of anti-PD-1 antibody (Ab) therapy in a transgenic model of melanoma.

Conference Journal of Clinical Oncology · May 20, 2017 3053 Background: Activation of the Wnt-β-catenin signaling pathway is associated with poor T cell infiltration of tumors. We have previously demonstrated that paracrine Wnt5a-β-catenin signaling is a critical trigger of dendritic ... Full text Cite

Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy.

Journal Article J Immunother Cancer · 2017 As cancer strikes, individuals vary not only in terms of factors that contribute to its occurrence and development, but as importantly, in their capacity to respond to treatment. While exciting new therapeutic options that mobilize the immune system agains ... Full text Open Access Link to item Cite

Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab.

Journal Article Int J Radiat Oncol Biol Phys · September 1, 2016 PURPOSE: Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination. METHODS ... Full text Link to item Cite

Isolated recto-sigmoid colitis: a new imaging pattern of ipilimumab-associated colitis.

Journal Article Abdom Radiol (NY) · February 2016 PURPOSE: The purpose of this study is to describe typical CT findings and distinct imaging patterns of ipilimumab-associated colitis in immunotherapeutic treatment of melanoma. MATERIALS AND METHODS: This HIPAA-compliant retrospective study included 86 pat ... Full text Link to item Cite

Immune evasion pathways and the design of dendritic cell-based cancer vaccines.

Journal Article Discov Med · February 2016 Emerging data is suggesting that the process of dendritic cell (DC) tolerization is an important step in tumorigenesis. Our understanding of the networks within the tumor microenvironment that functionally tolerize DC function is evolving while methods for ... Open Access Link to item Cite

Genetic risk analysis of a patient with fulminant autoimmune type 1 diabetes mellitus secondary to combination ipilimumab and nivolumab immunotherapy.

Journal Article J Immunother Cancer · 2016 BACKGROUND: Checkpoint inhibitor immunotherapy is becoming an effective treatment modality for an increasing number of malignancies. As a result, autoinflammatory side-effects are also being observed more commonly in the clinic. We are currently unable to ... Full text Open Access Link to item Cite

Melanoma-Derived Wnt5a Promotes Local Dendritic-Cell Expression of IDO and Immunotolerance: Opportunities for Pharmacologic Enhancement of Immunotherapy.

Journal Article Cancer Immunol Res · September 2015 The β-catenin signaling pathway has been demonstrated to promote the development of a tolerogenic dendritic cell (DC) population capable of driving regulatory T-cell (Treg) differentiation. Further studies have implicated tolerogenic DCs in promoting carci ... Full text Open Access Link to item Cite

Rapid complete response of metastatic melanoma in a patient undergoing ipilimumab immunotherapy in the setting of active ulcerative colitis.

Journal Article J Immunother Cancer · 2015 While blockade of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) T cell regulatory receptor has become a commonly utilized strategy in the management of advanced melanoma, many questions remain regarding the use of this agent in patient populations with aut ... Full text Open Access Link to item Cite

Immunotherapy following regional chemotherapy treatment of advanced extremity melanoma.

Journal Article Ann Surg Oncol · August 2014 PURPOSE: Following regional chemotherapy (RC) for melanoma, approximately 75 % of patients will progress. The role of immunotherapy after RC has not been well established. METHODS: A prospective, single-institution database of 243 patients with in-transit ... Full text Link to item Cite

Early Carcinogenesis Involves the Establishment of Immune Privilege via Intrinsic and Extrinsic Regulation of Indoleamine 2,3-dioxygenase-1: Translational Implications in Cancer Immunotherapy.

Journal Article Front Immunol · 2014 Although prolonged genetic pressure has been conjectured to be necessary for the eventual development of tumor immune evasion mechanisms, recent work is demonstrating that early genetic mutations are capable of moonlighting as both intrinsic and extrinsic ... Full text Open Access Link to item Cite

Type III TGF-β receptor downregulation generates an immunotolerant tumor microenvironment.

Journal Article J Clin Invest · September 2013 Featured Publication Cancers subvert the host immune system to facilitate disease progression. These evolved immunosuppressive mechanisms are also implicated in circumventing immunotherapeutic strategies. Emerging data indicate that local tumor-associated DC populations exhibi ... Full text Open Access Link to item Cite

Improved time to progression for transarterial chemoembolization compared with transarterial embolization for patients with unresectable hepatocellular carcinoma.

Journal Article Clin Colorectal Cancer · September 2012 BACKGROUND: Embolizing branches of the hepatic artery lengthens survival for patients with unresectable hepatocellular carcinoma (HCC), but the benefit of combining chemotherapy with the embolizing particles remains controversial. METHODS: A retrospective ... Full text Link to item Cite

Abstract 3548: Loss of the type III TGF-β receptor during cancer progression generates an immunotolerant tumor microenvironment: Translational implications for TGF-β inhibition and immunotherapy biomarker development

Journal Article Cancer Research · April 15, 2012 AbstractWe have demonstrated that the type III TGF-β receptor (TβRIII) functions to suppress cancer progression and is downregulated in several malignancies. Previous work has shown TβRIII to undergo ectodom ... Full text Cite

Role of the type III TGF-β receptor in modulating antitumor immunity during breast cancer progression.

Journal Article J Clin Oncol · May 20, 2011 10540 Background: We have shown that breast cancers downregulate the expression of the type III TGF-β receptor (TβRIII) tumor suppressor during tumor progression. Previous work has shown TβRIII to undergo ectodomain shedding, enabling the sequestration of ... Link to item Cite

Pharmacological inhibition of TGFβ as a strategy to augment the antitumor immune response.

Journal Article Curr Opin Investig Drugs · December 2010 Featured Publication There is considerable evidence suggesting that a variety of malignancies utilize the TGFβ cytokine to evade immune surveillance mechanisms to facilitate tumor growth and metastatic progression. The recently developed large- and small-molecule TGFβ inhibito ... Link to item Cite

The efficacy and tolerability of transarterial chemo-embolization (TACE) compared with transarterial embolization (TAE) for patients with unresectable hepatocellular carcinoma (HCC).

Journal Article J Clin Oncol · May 20, 2008 4595 Background: Radiologic procedures that involve embolizing branches of the hepatic artery lengthen survival for patients with unresectable HCC, but the benefit of administering intrahepatic arterial chemotherapy during the embolization procedure is unc ... Link to item Cite

Enhanced activation of human dendritic cells by inducible CD40 and Toll-like receptor-4 ligation.

Journal Article Cancer Res · November 1, 2007 Featured Publication Despite the potency of dendritic cells (DC) as antigen-presenting cells for priming adaptive immunity, DC-based cancer vaccines have been largely insufficient to effectively reduce tumor burden or prevent tumor progression in most patients. To enhance DC-b ... Full text Link to item Cite

Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo.

Journal Article Nat Med · February 2005 Featured Publication Modest clinical outcomes of dendritic-cell (DC) vaccine trials call for the refinement of DC vaccine design. Although many potential antigens have been identified, development of methods to enhance antigen presentation by DCs has lagged. We have engineered ... Full text Link to item Cite

Template-based docking of a prolactin receptor proline-rich motif octapeptide to FKBP12: implications for cytokine receptor signaling.

Journal Article Protein Sci · May 1997 A conserved proline-rich motif (PRM) in the cytoplasmic domain of cytokine receptors has been suggested to be a signaling switch regulated by the action of the FK506 binding protein (FKBP) family of peptidylprolyl isomerases (O'Neal KD, Yu-Lee LY, Shearer ... Full text Link to item Cite

Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase.

Journal Article Biochemistry · November 12, 1996 Carbamoyl phosphate synthetase (CPS) catalyzes the formation of carbamoyl phosphate from glutamine, bicarbonate, and 2 mol of MgATP. The heterodimeric protein is composed of a small amidotransferase subunit and a larger synthetase subunit. The synthetase s ... Full text Link to item Cite

Comparison of the functional differences for the homologous residues within the carboxy phosphate and carbamate domains of carbamoyl phosphate synthetase.

Journal Article Biochemistry · November 12, 1996 Carbamoyl phosphate synthetase (CPS) from Escherichia coli catalyzes the formation of carbamoyl phosphate from two molecules of MgATP, bicarbonate, and glutamine. It has been previously shown that the amino- and carboxy-terminal halves of the large subunit ... Full text Link to item Cite

Structural Fluctuations of a Cryptophane Host:  A Molecular Dynamics Simulation

Journal Article Journal of the American Chemical Society · January 1, 1996 Full text Cite