Scholars@Duke
Qi-Jing Li

Qi-Jing Li

Adjunct Associate Professor in the Department of Immunology
Integrative Immunobiology
qi-jing.li@duke.edu
Box 3010 DUMC, 303 Jones Building, Durham, NC 27710
303 Jones Building, 207 Resear, Box 3010 DUMC, Durham, NC 27710

Selected Publications

DNASE1L3-expressing dendritic cells promote CD8+ T cell function and anti-PD-(L)1 therapy efficacy by degrading neutrophil extracellular traps.

Journal Article Cancer Cell · September 8, 2025 CD8+ T cell exclusion and dysfunction in the tumor microenvironment (TME) are among the most challenging obstacles for anti-PD-(L)1 therapy. Here, we report that tumor-infiltrating dendritic cell (DC)-specific expression of the deoxyribonuclease, DNASE1L3, ... Full text Link to item Cite

Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts.

Journal Article Cancer Cell · June 9, 2025 Bone metastatic lesions typically associate with suboptimal responses to immune checkpoint blockade (ICB) therapies. In this study, we observed that across multiple clinical cohorts and a variety of mouse models, the presence of osseous metastases induces ... Full text Link to item Cite

Supercharging CAR-T cells through transcriptional and epigenetic armoring.

Journal Article Theranostics · 2025 Inspired by the remarkable success of CAR-T therapy in hematologic malignancies, research is increasingly focused on adapting this treatment for solid tumors. However, CAR-T efficacy remains limited due to its exhaustion and shortened persistence. Transcri ... Full text Link to item Cite

B-Lightning: using bait genes for marker gene hunting in single-cell data with complex heterogeneity.

Journal Article Brief Bioinform · November 22, 2024 In single-cell studies, cells can be characterized with multiple sources of heterogeneity (SOH) such as cell type, developmental stage, cell cycle phase, activation state, and so on. In some studies, many nuisance SOH are of no interest, but may confound t ... Full text Link to item Cite

Nuclear receptor-SINE B1 network modulates expanded pluripotency in blastoids and blastocysts.

Journal Article Nat Commun · November 19, 2024 Embryonic stem cells possess the remarkable ability to self-organize into blastocyst-like structures upon induction. These stem cell-based embryo models serve as invaluable platforms for studying embryogenesis and therapeutic developments. Nevertheless, th ... Full text Link to item Cite

IL-1 signaling in aging and cancer: An inflammaging feedback loop unveiled.

Journal Article Cancer Cell · November 11, 2024 In a Science paper, Park et al. identified interleukin (IL)-1α as a key driver of positive feedback in inflammaging, linking aging-associated downregulation of DNMT3A to increased IL-1α production in lung myeloid cells. This triggers emergency myelopoiesis ... Full text Link to item Cite

Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response.

Journal Article Nat Commun · October 3, 2024 Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic r ... Full text Open Access Link to item Cite

Necroptosis stimulates interferon-mediated protective anti-tumor immunity.

Journal Article Cell Death Dis · June 10, 2024 Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tu ... Full text Link to item Cite

SifiNet: a robust and accurate method to identify feature gene sets and annotate cells.

Journal Article Nucleic Acids Res · May 22, 2024 SifiNet is a robust and accurate computational pipeline for identifying distinct gene sets, extracting and annotating cellular subpopulations, and elucidating intrinsic relationships among these subpopulations. Uniquely, SifiNet bypasses the cell clusterin ... Full text Link to item Cite

SifiNet: A robust and accurate method to identify feature gene sets and annotate cells.

Journal Article bioRxiv · April 6, 2024 SifiNet is a robust and accurate computational pipeline for identifying distinct gene sets, extracting and annotating cellular subpopulations, and elucidating intrinsic relationships among these subpopulations. Uniquely, SifiNet bypasses the cell clusterin ... Full text Link to item Cite

Breaking NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection.

Journal Article Nat Immunol · February 2024 Melanoma cells, deriving from neuroectodermal melanocytes, may exploit the nervous system's immune privilege for growth. Here we show that nerve growth factor (NGF) has both melanoma cell intrinsic and extrinsic immunosuppressive functions. Autocrine NGF e ... Full text Open Access Link to item Cite

Branched-Chain Amino Acid Accumulation Fuels the Senescence-Associated Secretory Phenotype.

Journal Article Adv Sci (Weinh) · January 2024 The essential branched-chain amino acids (BCAAs) leucine, isoleucine, and valine play critical roles in protein synthesis and energy metabolism. Despite their widespread use as nutritional supplements, BCAAs' full effects on mammalian physiology remain unc ... Full text Open Access Link to item Cite

Necroptosis Stimulates Interferon-Mediated Protective Anti-Tumor Immunity.

Journal Article Res Sq · December 19, 2023 Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tu ... Full text Link to item Cite

Single-nucleus multiomic mapping of m6A methylomes and transcriptomes in native populations of cells with sn-m6A-CT.

Journal Article Mol Cell · August 25, 2023 N6-methyladenosine (m6A) RNA modification plays important roles in the governance of gene expression and is temporally regulated in different cell states. In contrast to global m6A profiling in bulk sequencing, single-cell technologies for analyzing m6A he ... Full text Link to item Cite

Antagonizing the irreversible thrombomodulin-initiated proteolytic signaling alleviates age-related liver fibrosis via senescent cell killing.

Journal Article Cell Res · July 2023 Cellular senescence is a stress-induced, stable cell cycle arrest phenotype which generates a pro-inflammatory microenvironment, leading to chronic inflammation and age-associated diseases. Determining the fundamental molecular pathways driving senescence ... Full text Open Access Link to item Cite

GABAergic signaling beyond synapses: an emerging target for cancer therapy.

Journal Article Trends Cell Biol · May 2023 Traditionally, γ-aminobutyric acid (GABA) is best known for its role as a primary inhibitory neurotransmitter reducing neuronal excitability in the mammalian central nervous system (CNS), thereby producing calming effects. However, an emerging body of data ... Full text Open Access Link to item Cite

Neural mechanism underlying depressive-like state associated with social status loss.

Journal Article Cell · February 2, 2023 Downward social mobility is a well-known mental risk factor for depression, but its neural mechanism remains elusive. Here, by forcing mice to lose against their subordinates in a non-violent social contest, we lower their social ranks stably and induce de ... Full text Link to item Cite

CD200+ cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti-PD-1/PD-L1 therapy.

Journal Article Sci Transl Med · January 18, 2023 Anti-PD-1/PD-L1 therapy, either by anti-PD-1 antibody or anti-PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8+ T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8+ T cell populations. Hence, th ... Full text Link to item Cite

Clustering Deviation Index (CDI): a robust and accurate internal measure for evaluating scRNA-seq data clustering.

Journal Article Genome Biol · December 27, 2022 Most single-cell RNA sequencing (scRNA-seq) analyses begin with cell clustering; thus, the clustering accuracy considerably impacts the validity of downstream analyses. In contrast with the abundance of clustering methods, the tools to assess the clusterin ... Full text Link to item Cite

Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy.

Journal Article Cancer Cell · June 13, 2022 Featured Publication Despite the unprecedented success of immune checkpoint inhibitors (ICIs) as anti-cancer therapy, it remains a prevailing clinical need to identify additional mechanisms underlying ICI therapeutic efficacy and potential drug resistance. Here, using lineage ... Full text Link to item Cite

IFI16-STING-NF-κB signaling controls exogenous mitochondrion-induced endothelial activation.

Journal Article Am J Transplant · June 2022 Mitochondria released from injured cells activate endothelial cells (ECs), fostering inflammatory processes, including allograft rejection. The stimulator of interferon genes (STING) senses endogenous mitochondrial DNA, triggering innate immune activation ... Full text Open Access Link to item Cite

Cancer-cell-derived GABA promotes β-catenin-mediated tumour growth and immunosuppression.

Journal Article Nat Cell Biol · February 2022 Featured Publication Many cancers have an unusual dependence on glutamine. However, most previous studies have focused on the contribution of glutamine to metabolic building blocks and the energy supply. Here, we report that cancer cells with aberrant expression of glutamate d ... Full text Open Access Link to item Cite

CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis.

Journal Article Cell Mol Immunol · December 2021 Regulatory T cell (Treg) stability is necessary for the proper control of immune activity and tissue homeostasis. However, it remains unclear whether Treg stability must be continually reinforced or is established during development under physiological con ... Full text Link to item Cite

Resident memory T cells in tumor-distant tissues fortify against metastasis formation.

Journal Article Cell Rep · May 11, 2021 Featured Publication As a critical machinery for rapid pathogen removal, resident memory T cells (TRMs) are locally generated after the initial encounter. However, their development accompanying tumorigenesis remains elusive. Using a murine breast cancer model, we show that TR ... Full text Link to item Cite

A conjoined universal helper epitope can unveil antitumor effects of a neoantigen vaccine targeting an MHC class I-restricted neoepitope.

Journal Article NPJ Vaccines · January 18, 2021 Personalized cancer vaccines targeting neoantigens arising from somatic missense mutations are currently being evaluated for the treatment of various cancers due to their potential to elicit a multivalent, tumor-specific immune response. Several cancers ex ... Full text Open Access Link to item Cite

Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage.

Journal Article Cell Mol Immunol · January 2021 Featured Publication CD4+ and CD8+ T cells are dichotomous lineages in adaptive immunity. While conventionally viewed as distinct fates that are fixed after thymic development, accumulating evidence indicates that these two populations can exhibit significant lineage plasticit ... Full text Link to item Cite

Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy.

Journal Article Sci Adv · January 2021 Featured Publication The efficacy of cancer immunotherapy is dictated by CD8+ T cell infiltration and the nature of the tumor microenvironment (TME). By inflaming the TME to favor CD8+ T cell immunity, radiation is now widely considered as a neoadjuvant for immunomodulation. H ... Full text Link to item Cite

Peripheral eosinophil counts predict efficacy of anti-CD19 CAR-T cell therapy against B-lineage non-Hodgkin lymphoma.

Journal Article Theranostics · 2021 Featured Publication Rationale: The onset of cytokine release syndrome (CRS) and in vivo persistence of anti-CD19 chimeric antigen receptor T (CAR-T) cells after infusion correlate with clinical responsiveness. However, there are no known baseline biomarkers that can predict t ... Full text Link to item Cite

TCR repertoire characteristics predict clinical response to adoptive CTL therapy against nasopharyngeal carcinoma.

Journal Article Oncoimmunology · 2021 The past decade has witnessed the gradual and steady progress of adoptive T cell therapy in treating various types of cancer. In combination with gemcitabine and carboplatin chemotherapy, we previously conducted a clinical trial, NCT00690872, to treat Epst ... Full text Link to item Cite

A mosaic analysis system with Cre or Tomato expression in the mouse.

Journal Article Proc Natl Acad Sci U S A · November 10, 2020 Featured Publication Somatic mutations are major genetic contributors to cancers and many other age-related diseases. Many disease-causing somatic mutations can initiate clonal growth prior to the appearance of any disease symptoms, yet experimental models that can be used to ... Full text Link to item Cite

Potential lung attack and lethality generated by EpCAM-specific CAR-T cells in immunocompetent mouse models.

Journal Article Oncoimmunology · August 15, 2020 Featured Publication The tumoricidal efficiency of human CAR-T cells is generally evaluated using immune-deficient mouse models; however, due to their immune-incompetency and the species-specific reactivity of a target antigen, these models are problematic to imitate CAR-T-ind ... Full text Link to item Cite

Synthesis and Biological Evaluation of Subglutinol Analogs for Immunomodulatory Agents.

Journal Article J Med Chem · January 9, 2020 Autoimmune diseases are chronic inflammatory diseases associated with high morbidity and mortality. Treatment options for autoimmune diseases have increased over the past several decades, but they are, in general, limited in their clinical efficacy due to ... Full text Link to item Cite

T cell receptor repertoire as a prognosis marker for heat shock protein peptide complex-96 vaccine trial against newly diagnosed glioblastoma.

Journal Article Oncoimmunology · 2020 Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a dismal prognosis. We previously reported that vaccination with heat shock protein peptide complex-96 (HSPPC-96) improves survival in patients with newly diagnos ... Full text Link to item Cite

VisTCR: An Interactive Software for T Cell Repertoire Sequencing Data Analysis.

Journal Article Front Genet · 2020 Recent progress in high throughput sequencing technologies has provided an opportunity to probe T cell receptor (TCR) repertoire, bringing about an explosion of TCR sequencing data and analysis tools. For easier and more heuristic analysis TCR sequencing d ... Full text Link to item Cite

Putative biomarkers for predicting tumor sample purity based on gene expression data.

Journal Article BMC Genomics · December 27, 2019 BACKGROUND: Tumor purity is the percent of cancer cells present in a sample of tumor tissue. The non-cancerous cells (immune cells, fibroblasts, etc.) have an important role in tumor biology. The ability to determine tumor purity is important to understand ... Full text Link to item Cite

Microrna-191 Regulates T-Cell Clonal Expansion during Graft-Versus-Host Disease

Conference Blood · November 13, 2019 Allogeneic hematopoietic cell transplantation is a potentially curative treatment choice for a wide variety of hematological malignancies. However, graft-versus-host disease (GVHD), which is mediated by donor alloreactive T cells, limits the succes ... Full text Cite

TCR repertoire and CDR3 motif analyses depict the role of αβ T cells in Ankylosing spondylitis.

Journal Article EBioMedicine · September 2019 Featured Publication BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease with worldwide high prevalence. Although AS is strongly associated with HLA-B27 MHC-I antigen presentation, the role played by αβ T cells in AS remains elusive. METHODS: Utilizing TC ... Full text Link to item Cite

HLA class II-Restricted CD8+ T cells in HIV-1 Virus Controllers.

Journal Article Sci Rep · July 15, 2019 A paradigm shifting study demonstrated that induction of MHC class E and II-restricted CD8+ T cells was associated with the clearance of SIV infection in rhesus macaques. Another recent study highlighted the presence of HIV-1-specific class II-restricted C ... Full text Open Access Link to item Cite

Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation.

Journal Article Nat Commun · June 3, 2019 Enhancer of zeste homolog 2 (EZH2)-mediated trimethylation of histone 3 lysine 27 (H3K27Me3) is critical for immune regulation. However, evidence is lacking to address the effect of EZH2 enzyme's activity on intestinal immune responses during inflammatory ... Full text Link to item Cite

Lineage Tracking the Generation of T Regulatory Cells From Microbial Activated T Effector Cells in Naïve Mice.

Journal Article Front Immunol · 2019 Regulatory T cells (Tregs) are essential for the maintenance of gut homeostasis by suppressing conventional CD4+ helper T cells (Tconvs) that are activated by microbial antigens. Although thymus is the major source of the peripheral Tregs, peripheral conve ... Full text Link to item Cite

Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer.

Journal Article Nat Commun · December 18, 2018 Featured Publication Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses of 15 patients with non-small cell lung cancer (NSCLC). This re ... Full text Link to item Cite

Synthetic lethality between HER2 and transaldolase in intrinsically resistant HER2-positive breast cancers.

Journal Article Nat Commun · October 15, 2018 Intrinsic resistance to anti-HER2 therapy in breast cancer remains an obstacle in the clinic, limiting its efficacy. However, the biological basis for intrinsic resistance is poorly understood. Here we performed a CRISPR/Cas9-mediated loss-of-function gene ... Full text Open Access Link to item Cite

Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells.

Journal Article Nat Med · October 2018 Featured Publication Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection1-3. This has been largely attributed to chemotherapy-induced impairment of innat ... Full text Link to item Cite

Abstract 2255: Using tumor sample gene expression data to infer tumor purity levels with stochastic gradient boosting machines

Conference Cancer Research · July 1, 2018 AbstractTumor purity is the percent of cancer cells present in a sample of tumor tissue. The noncancerous cells (stromal cells) in a tumor are thought to have an important role in tumor growth, metastatic pr ... Full text Cite

CD36 initiates the secretory phenotype during the establishment of cellular senescence.

Journal Article EMBO Rep · June 2018 Featured Publication Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular me ... Full text Link to item Cite

In Vivo Expansion and Antitumor Activity of Coinfused CD28- and 4-1BB-Engineered CAR-T Cells in Patients with B Cell Leukemia.

Journal Article Mol Ther · April 4, 2018 Featured Publication Several recent clinical trials have successfully incorporated a costimulatory domain derived from either CD28 or 4-1BB with the original CD3ζ T cell activating domain to form second-generation chimeric antigen receptors (CARs) that can increase the respons ... Full text Link to item Cite

Control of Intestinal Inflammation, Colitis-Associated Tumorigenesis, and Macrophage Polarization by Fibrinogen-Like Protein 2.

Journal Article Front Immunol · 2018 Fibrinogen-like protein 2 (Fgl2) is critical for immune regulation in the inflammatory state. Elevated Fgl2 levels are observed in patients with inflammatory bowel disease (IBD), but little is known about its functional significance. In this study, we soug ... Full text Link to item Cite

CD27 stimulation unveils the efficacy of linked class I/II peptide vaccines in poorly immunogenic tumors by orchestrating a coordinated CD4/CD8 T cell response.

Journal Article Oncoimmunology · 2018 Despite their promise, tumor-specific peptide vaccines have limited efficacy. CD27 is a costimulatory molecule expressed on CD4+ and CD8+ T cells that is important in immune activation. Here we determine if a novel CD27 agonist antibody (αhCD27) can enhanc ... Full text Link to item Cite

Identification of a serum microRNA expression signature for detection of lung cancer, involving miR-23b, miR-221, miR-148b and miR-423-3p.

Journal Article Lung Cancer · December 2017 OBJECTIVES: Serum mircoRNAs (miRNAs), with their noticeable stability and unique expression pattern in patients with various diseases, are powerful novel non-invasive biomarkers for cancer detection. The objective of this study was to identify specific ser ... Full text Link to item Cite

[Relationship between Helicobacter pylori infection and miR-24-3p expression during the development of gastric mucosa lesions].

Journal Article Zhonghua Yi Xue Za Zhi · September 26, 2017 Objectives: To explore the expression of micro RNA-24-3p (miR-24-3p) in different gastric mucosa lesions, and analyze the potential correlation between Helicobacter pylori (H.pylori) infection and miR-24-3p expression in different gastric lesions. Methods: ... Full text Link to item Cite

Collaboration between Distinct Rab Small GTPase Trafficking Circuits Mediates Bacterial Clearance from the Bladder Epithelium.

Journal Article Cell Host Microbe · September 13, 2017 Rab small GTPases control membrane trafficking through effectors that recruit downstream mediators such as motor proteins. Subcellular trafficking typically involves multiple Rabs, with each specific step mediated by a distinct Rab protein. We describe a c ... Full text Link to item Cite

Tumor stem cell RNA-leaded dedritic cell vaccine for recurrent glioblastoma: a phase 1 trail.

Conference Neurology · April 27, 2017 Objective: To evaluate the feasibility and safety of administering brain tumor stem cell (BTSC) mRNA-loaded dendritic cells (DC) to patients with recurrent GBM. Background: BTSC CD133+ contribute to GBM propagation and are associated with chemo-radiation ... Link to item Cite

UHRF1 is required for basal stem cell proliferation in response to airway injury.

Journal Article Cell Discov · 2017 Cellular senescence is a cell fate characterized by an irreversible cell cycle arrest, but the molecular mechanism underlying this senescence hallmark remains poorly understood. Through an unbiased search for novel senescence regulators in airway basal cel ... Full text Open Access Link to item Cite

Blocking C5aR signaling promotes the anti-tumor efficacy of PD-1/PD-L1 blockade.

Journal Article Oncoimmunology · 2017 Anti-PD-1/PD-L1 therapy has achieved great success in the clinic; however, only a small fraction of cancer patient benefit from PD-1/PD-L1 blockade therapy, and overcoming resistance to PD-1/PD-L1 blockade has thus become a primary priority. In this study, ... Full text Link to item Cite

An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage.

Journal Article Nat Neurosci · December 2016 Inflammation induced by innate immunity influences the development of T cell-mediated autoimmunity in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). We found that strong activation of innate immunity induced Nod-l ... Full text Link to item Cite

The MicroRNA miR-191 Supports T Cell Survival Following Common γ Chain Signaling.

Journal Article J Biol Chem · November 4, 2016 To ensure lifelong immunocompetency, naïve and memory T cells must be adequately maintained in the peripheral lymphoid tissues. Homeostatic maintenance of T cells is controlled by tonic signaling through T cell antigen receptors and common γ chain cytokine ... Full text Link to item Cite

Interleukin-2 reverses CD8(+) T cell exhaustion in clinical malignant pleural effusion of lung cancer.

Journal Article Clin Exp Immunol · October 2016 Malignant pleural effusion (MPE) is a poor prognostic sign for cancer patients, whereas the functional condition of MPE CD8(+) T cells is unknown. Intracavitary immunotherapy with interleukin (IL)-2 has been proven effective in controlling MPE. To elucidat ... Full text Link to item Cite

Glimpse of natural selection of long-lived T-cell clones in healthy life.

Journal Article Proc Natl Acad Sci U S A · August 30, 2016 Featured Publication Homeostatic maintenance of T cells with broad clonal diversity is influenced by both continuing output of young T cells from the thymus and ongoing turnover of preexisting clones in the periphery. In the absence of infection, self and commensal antigens ar ... Full text Link to item Cite

Unexpected positive control of NFκB and miR-155 by DGKα and ζ ensures effector and memory CD8+ T cell differentiation.

Journal Article Oncotarget · June 7, 2016 Signals from the T-cell receptor (TCR) and γ-chain cytokine receptors play crucial roles in initiating activation and effector/memory differentiation of CD8 T-cells. We report here that simultaneous deletion of both diacylglycerol kinase (DGK) α and ζ (DKO ... Full text Link to item Cite

Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.

Journal Article Cancer Res · April 15, 2016 Featured Publication Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results hav ... Full text Link to item Cite

MiR-148a functions to suppress metastasis and serves as a prognostic indicator in triple-negative breast cancer.

Journal Article Oncotarget · April 12, 2016 Triple-negative breast cancer (TNBC) presents a major challenge in the clinic due to its lack of reliable prognostic markers and targeted therapies. Accumulating evidence strongly supports the notion that microRNAs (miRNAs) are involved in tumorigenesis an ... Full text Link to item Cite

MicroRNA-23a Curbs Necrosis during Early T Cell Activation by Enforcing Intracellular Reactive Oxygen Species Equilibrium.

Journal Article Immunity · March 15, 2016 Featured Publication Upon antigen engagement, augmented cytosolic reactive oxygen species (ROS) are needed to achieve optimal T cell receptor (TCR) signaling. However, uncontrolled ROS production is a prominent cause of necrosis, which elicits hyper-inflammation and tissue dam ... Full text Link to item Cite

Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment.

Journal Article Immunity · February 16, 2016 Featured Publication Dendritic cells (DCs) orchestrate complex membrane trafficking through an interconnected transportation network linked together by Rab GTPases. Through a tandem affinity purification strategy and mass spectrometry, we depicted an interactomic landscape of ... Full text Link to item Cite

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.

Journal Article Cancer Cell · January 11, 2016 The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit t ... Full text Open Access Link to item Cite

The tumor microenvironment disarms CD8+ T lymphocyte function via a miR-26a-EZH2 axis.

Journal Article Oncoimmunology · 2016 One of the most important factors that limit the potency of CD8+ cytotoxic T lymphocyte (CTL) responses is the tumor microenvironment (TME). Here, we provide evidence that miR-26a is a negative regulator of CTL function in the TME. Specifically, we identif ... Full text Link to item Cite

Targeting the Wnt-Regulatory Protein CTNNBIP1 by microRNA-214 Enhances the Stemness and Self-Renewal of Cancer Stem-Like Cells in Lung Adenocarcinomas.

Journal Article Stem Cells · December 2015 A novel hypothesis in cancer biology proposes that cancer growth is driven by cancer stem-like cells (CSLCs), also called tumor-initiating cells, which can self-renew and differentiate into multilineage progeny in a fashion similar to stem cells. However, ... Full text Link to item Cite

microRNA-214 promotes epithelial-mesenchymal transition and metastasis in lung adenocarcinoma by targeting the suppressor-of-fused protein (Sufu).

Journal Article Oncotarget · November 17, 2015 Distant metastasis is the major cause of cancer-related deaths in patients with lung adenocarcinoma (LAD). Emerging evidence reveals that miRNA is critical for tumor metastasis. miR-214 expression has been associated with LAD progression. However, whether ... Full text Link to item Cite

MicroRNA-17-92 controls T-cell responses in graft-versus-host disease and leukemia relapse in mice.

Journal Article Blood · September 10, 2015 MicroRNAs (miRs) play important roles in orchestrating many aspects of the immune response. The miR-17-92 cluster, which encodes 6 miRs including 17, 18a, 19a, 20a, 19b-1, and 92-1, is among the best characterized of these miRs. The miR-17-92 cluster has b ... Full text Link to item Cite

Regulation of T cell function by microRNA-720.

Journal Article Sci Rep · July 22, 2015 Chronic hepatitis B virus (HBV) infection is a major global health burden. Functional exhaustion and numerical reduction of HBV-specific cytotoxic T lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity in patients with chronic H ... Full text Link to item Cite

MicroRNA-31 negatively regulates peripherally derived regulatory T-cell generation by repressing retinoic acid-inducible protein 3.

Journal Article Nat Commun · July 13, 2015 Peripherally derived regulatory T (pT(reg)) cell generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. Here we show that TCR signalling induces the microRNA miR-31, which negatively regulates pT(reg)-cell generation. miR-3 ... Full text Link to item Cite

Association of CD8(+) T lymphocyte repertoire spreading with the severity of DRESS syndrome.

Journal Article Sci Rep · April 23, 2015 T-cell receptor (TCR)-mediated cross-recognition is a major mechanism in the pathogenesis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. However, the characteristics of the TCR repertoire and the clinical significance of reperto ... Full text Link to item Cite

Diversity index of mucosal resident T lymphocyte repertoire predicts clinical prognosis in gastric cancer.

Journal Article Oncoimmunology · April 2015 Featured Publication A characteristic immunopathology of human cancers is the induction of tumor antigen-specific T lymphocyte responses within solid tumor tissues. Current strategies for immune monitoring focus on the quantification of the density and differentiation status o ... Full text Open Access Link to item Cite

miR-23a blockade enhances adoptive T cell transfer therapy by preserving immune-competence in the tumor microenvironment.

Journal Article Oncoimmunology · March 2015 In adoptive T cell transfer therapy (ACT), the antitumor efficacy of cytotoxic CD8+ T lymphocytes (CTLs) has been limited by tumor-induced immunosuppression. We have demonstrated that miR-23a blockade in tumor-specific CTLs conferred resilience to TGFβ-med ... Full text Link to item Cite

Targeting miR-23a in CD8+ cytotoxic T lymphocytes prevents tumor-dependent immunosuppression.

Journal Article J Clin Invest · December 2014 Featured Publication CD8(+) cytotoxic T lymphocytes (CTLs) have potent antitumor activity and therefore are leading candidates for use in tumor immunotherapy. The application of CTLs for clinical use has been limited by the susceptibility of ex vivo-expanded CTLs to become dys ... Full text Link to item Cite

miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways.

Journal Article J Clin Invest · October 2014 Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Glioma-initiating cells (GICs) are stem-like cells that have been implicated in glioblastoma progression and recurrence; however, the distinct properties of GICs and non-GICs within GB ... Full text Link to item Cite

MeCP2 enforces Foxp3 expression to promote regulatory T cells' resilience to inflammation.

Journal Article Proc Natl Acad Sci U S A · July 8, 2014 Featured Publication Forkhead box P3(+) (Foxp3(+)) regulatory T cells (Tregs) are crucial for peripheral tolerance. During inflammation, steady Foxp3 expression in Tregs is essential for maintaining their lineage identity and suppressive function. However, the molecular machin ... Full text Link to item Cite

Biological evaluation of subglutinol a as a novel immunosuppressive agent for inflammation intervention.

Journal Article ACS Med Chem Lett · May 8, 2014 Subglutinol A (1) is an immunosuppressive natural product isolated from Fusarium subglutinans, an endophytic fungus from the vine Tripterygium wilfordii. We show that 1 exerts multimodal immune-suppressive effects on activated T cells in vitro: subglutinol ... Full text Link to item Cite

miR-17-92 cluster targets phosphatase and tensin homology and Ikaros Family Zinc Finger 4 to promote TH17-mediated inflammation.

Journal Article J Biol Chem · May 2, 2014 Featured Publication The miR-17-92 cluster regulates a broad spectrum of biological processes of T cell immunity. This cluster was found to facilitate T cell proliferation, enhance antitumor activities and promote T cell-dependent antibody responses. However, little is known a ... Full text Link to item Cite

MeCP2 reinforces STAT3 signaling and the generation of effector CD4+ T cells by promoting miR-124-mediated suppression of SOCS5.

Journal Article Sci Signal · March 11, 2014 Featured Publication Methyl CpG binding protein 2 (MeCP2) is an X-linked, multifunctional epigenetic regulator that is best known for its role in the neurological disorder Rett syndrome; however, it is also linked to multiple autoimmune disorders. We examined a potential role ... Full text Link to item Cite

A single peptide-major histocompatibility complex ligand triggers digital cytokine secretion in CD4(+) T cells.

Journal Article Immunity · November 14, 2013 We have developed a single-molecule imaging technique that uses quantum-dot-labeled peptide-major histocompatibility complex (pMHC) ligands to study CD4(+) T cell functional sensitivity. We found that naive T cells, T cell blasts, and memory T cells could ... Full text Link to item Cite

Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host disease.

Journal Article Blood · November 7, 2013 Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Approximately 35% to 50% of HCT recipients develop aGVHD; however, there are no validated diagnostic and pred ... Full text Link to item Cite

Tracking proliferative history in lymphocyte development with cre-mediated sister chromatid recombination.

Journal Article PLoS Genet · October 2013 Tracking and isolating live cells based on their proliferative history in live animals remains a technical challenge in animal studies. We have designed a genetic marking system for tracking the proliferative frequency and history of lymphocytes during the ... Full text Link to item Cite

Transcriptomic analysis of peripheral blood mononuclear cells in rapid progressors in early HIV infection identifies a signature closely correlated with disease progression.

Journal Article Clin Chem · August 2013 Featured Publication BACKGROUND: A substantial percentage (10%-15%) of HIV-infected individuals experience a sharp decline in CD4(+) T-cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) vs chron ... Full text Link to item Cite

T cell receptor (TCR) and transforming growth factor β (TGF-β) signaling converge on DNA (cytosine-5)-methyltransferase to control forkhead box protein 3 (foxp3) locus methylation and inducible regulatory T cell differentiation.

Journal Article J Biol Chem · June 28, 2013 Featured Publication Naïve T cells can be induced to differentiate into Foxp3(+) regulatory T cells (iTregs) upon suboptimal T cell receptor (TCR) stimulus or TCR stimulus in conjunction with TGF-β signaling; however, we do not fully understand how these signals coordinately c ... Full text Link to item Cite

mir-17-92: a polycistronic oncomir with pleiotropic functions.

Journal Article Immunol Rev · May 2013 Neoplastic transformation is caused by accumulation of genetic lesions that ultimately convert normal cells into tumor cells with uncontrolled proliferation and survival, unlimited replicative potential, and invasive growth. Emerging evidence has highlight ... Full text Link to item Cite

miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis.

Journal Article Nat Cell Biol · March 2013 Featured Publication The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We repo ... Full text Link to item Cite

TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma.

Journal Article Cancer Cell · September 11, 2012 Featured Publication Portal vein tumor thrombus (PVTT) is strongly correlated to a poor prognosis for patients with hepatocellular carcinoma (HCC). In this study, we uncovered a causative link between hepatitis B virus (HBV) infection and development of PVTT. Mechanistically, ... Full text Link to item Cite

Transcriptional regulator Id2 is required for the CD4 T cell immune response in the development of experimental autoimmune encephalomyelitis.

Journal Article J Immunol · August 1, 2012 An effective immune response to Ag challenge is critically dependent on the size of the effector cell population generated from clonal activation of Ag-specific T cells. The transcription network involved in regulating the size of the effector population, ... Full text Link to item Cite

Role of LAT in the granule-mediated cytotoxicity of CD8 T cells.

Journal Article Mol Cell Biol · July 2012 Linker for activation of T cells (LAT) is a transmembrane adaptor protein that is essential to bridge T cell receptor (TCR) engagement to downstream signaling events. The indispensable role of LAT in thymocyte development and T cell activation has been wel ... Full text Link to item Cite

Distinct CD4+ helper T cells involved in primary and secondary responses to infection.

Journal Article Proc Natl Acad Sci U S A · June 12, 2012 Helper T cells are critical for protective immunity, CD8(+) T-cell memory, and CD4(+) recall responses, but whether the same or distinct CD4(+) T cells are involved in these responses has not been established. Here we describe two CD4(+) T cells, LLO118 an ... Full text Link to item Cite

Photocrosslinkable pMHC monomers stain T cells specifically and cause ligand-bound TCRs to be 'preferentially' transported to the cSMAC.

Journal Article Nat Immunol · June 3, 2012 The binding of T cell antigen receptors (TCRs) to specific complexes of peptide and major histocompatibility complex (pMHC) is typically of very low affinity, which necessitates the use of multimeric pMHC complexes to label T lymphocytes stably. We report ... Full text Link to item Cite

The Epstein-Barr virus (EBV)-induced tumor suppressor microRNA MiR-34a is growth promoting in EBV-infected B cells.

Journal Article J Virol · June 2012 Epstein-Barr virus (EBV) infection of primary human B cells drives their indefinite proliferation into lymphoblastoid cell lines (LCLs). B cell immortalization depends on expression of viral latency genes, as well as the regulation of host genes. Given the ... Full text Open Access Link to item Cite

Molecular dissection of the miR-17-92 cluster's critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation.

Journal Article Blood · November 17, 2011 Featured Publication Mir-17-92 encodes 6 miRNAs inside a single polycistronic transcript, the proper expression of which is critical for early B-cell development and lymphocyte homeostasis. However, during the T-cell antigen response, the physiologic function of endogenous miR ... Full text Link to item Cite

The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression.

Journal Article J Immunol · November 15, 2011 IL-7Rα-mediated signals are essential for naive T lymphocyte survival. Recent studies show that IL-7Rα is internalized and either recycled to cell surface or degraded. However, how the intracellular process of IL-7Rα trafficking is regulated is unclear. In ... Full text Link to item Cite

Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells.

Journal Article Integr Biol (Camb) · July 2011 Prostate cancer is the second leading cause of cancer-related deaths among US males. Pomegranate juice (PJ), a natural product, was shown in a clinical trial to inhibit progression of this disease. However, the underlying mechanisms involved in the anti-pr ... Full text Link to item Cite

microRNAs at the regulatory frontier: an investigation into how microRNAs impact the development and effector functions of CD4 T cells.

Journal Article Immunol Res · April 2011 CD4 T cells are an integral part of adaptive immunity. microRNAs have been identified as fundamental regulators of post-transcriptional programs and to play roles in T lymphocytes' development, differentiation, and effector functions. To better understand ... Full text Link to item Cite

Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes.

Journal Article J Immunol · February 1, 2011 Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular bulk degradation pathway that plays critical roles in eliminating intracellular pathogens, presenting endogenous Ags, and regulating T lymphocyte survival and ... Full text Link to item Cite

Functional development of the T cell receptor for antigen.

Journal Article Prog Mol Biol Transl Sci · 2010 Featured Publication For over three decades now, the T cell receptor (TCR) for antigen has not ceased to challenge the imaginations of cellular and molecular immunologists alike. T cell antigen recognition transcends every aspect of adaptive immunity: it shapes the T cell repe ... Full text Link to item Cite

miR-19 is a key oncogenic component of mir-17-92.

Journal Article Genes Dev · December 15, 2009 Featured Publication Recent studies have revealed the importance of multiple microRNAs (miRNAs) in promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent oncogenic activity. Genomic amplification and elevated expression of mir-17-92 occur in several human B-c ... Full text Link to item Cite

An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a.

Journal Article Nat Immunol · November 2009 Featured Publication Thymic positive selection is based on the interactions of T cell antigen receptors (TCRs) with self peptide-major histocompatibility complex (MHC) ligands, but the identity of selecting peptides for MHC class II-restricted TCRs and the functional consequen ... Full text Link to item Cite

The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment.

Journal Article Immunity · September 18, 2009 Follicular helper T (Tfh) cells provide selection signals to germinal center B cells, which is essential for long-lived antibody responses. High CXCR5 and low CCR7 expression facilitates their homing to B cell follicles and distinguishes them from T helper ... Full text Link to item Cite

The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.

Journal Article Blood · July 2, 2009 The Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76) is a cytosolic adaptor protein essential for thymocyte development and T-cell activation. It contains a sterile-alpha motif (SAM) domain, 3 phosphotyrosine motifs, a p ... Full text Link to item Cite

Spatial and temporal dynamics of T cell receptor signaling with a photoactivatable agonist.

Journal Article Immunity · July 2007 The precise timing of signals downstream of the T cell receptor (TCR) is poorly understood. To address this problem, we prepared major histocompatibility complexes containing an antigenic peptide that is biologically inert until exposed to ultraviolet (UV) ... Full text Link to item Cite

miR-181a is an intrinsic modulator of T cell sensitivity and selection.

Journal Article Cell · April 6, 2007 Featured Publication T cell sensitivity to antigen is intrinsically regulated during maturation to ensure proper development of immunity and tolerance, but how this is accomplished remains elusive. Here we show that increasing miR-181a expression in mature T cells augments the ... Full text Link to item Cite

T cells as a self-referential, sensory organ.

Journal Article Annu Rev Immunol · 2007 Featured Publication In light of recent data showing that both helper and cytotoxic T cells can detect even a single molecule of an agonist peptide-MHC, alphabeta T cells are clearly a type of sensory cell, comparable to any in the nervous system. In addition, endogenous (self ... Full text Link to item Cite

Agonist/endogenous peptide-MHC heterodimers drive T cell activation and sensitivity.

Journal Article Nature · March 10, 2005 Featured Publication Alphabeta T lymphocytes are able to detect even a single peptide-major histocompatibility complex (MHC) on the surface of an antigen-presenting cell. This is despite clear evidence, at least with CD4+ T cells, that monomeric ligands are not stimulatory. In ... Full text Link to item Cite

cCXCR1 is a receptor for cIL-8 (9E3/cCAF) and its N- and C-terminal peptides and is also activated by hIL-8 (CXCL8).

Journal Article J Leukoc Biol · March 2005 Chemokines are chemotactic cytokines that play important roles in immune responses and wound healing, as well as in pathological conditions such as chronic inflammation and tumorigenesis. The chemokines and their receptors are highly conserved and maintain ... Full text Link to item Cite

A new generation organ culture arising from cross-talk between multiple primary human cell types.

Journal Article FASEB J · February 2005 The inability to experiment directly on humans strongly constrains biomedical research, creating a great need to develop cultures that mimic human tissues and organs as experimental systems that can be used to directly understand and manipulate biological ... Full text Link to item Cite

CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse.

Journal Article Nat Immunol · August 2004 Featured Publication How T cells respond with extraordinary sensitivity to minute amounts of agonist peptide and major histocompatibility complex (pMHC) molecules on the surface of antigen-presenting cells bearing large numbers of endogenous pMHC molecules is not understood. H ... Full text Link to item Cite

The N- and C-terminal peptides of hIL8/CXCL8 are ligands for hCXCR1 and hCXCR2.

Journal Article FASEB J · April 2004 Featured Publication Chemokines are small cytokines that function in immune responses, wound healing, and pathological conditions such as chronic inflammation and tumorigenesis. This multifunctionality has been attributed primarily to ligand interaction with multiple or dimeri ... Full text Link to item Cite

Histochemical localization of the PBAN receptor in the pheromone gland of Heliothis peltigera.

Journal Article Peptides · September 2003 The presence of the pyrokinin (PK)/ Pheromone biosynthesis activating neuropeptide (PBAN) receptor in pheromone gland cells of Heliothis peltigera females was demonstrated, and its spatial distribution in the ovipositor was visualized with two photo-affini ... Full text Link to item Cite

MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300.

Journal Article EMBO J · January 15, 2003 Featured Publication CBP/p300 recruitment to enhancer-bound complexes is a key determinant in promoter activation by many transcription factors. We present a novel mechanism of activating such complexes and show that pre-assembled Elk-1-p300 complexes become activated followin ... Full text Link to item Cite

The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue.

Journal Article BMC Cell Biol · June 10, 2002 BACKGROUND: During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and a ... Full text Link to item Cite

The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue.

Journal Article BMC cell biology [electronic resource] · June 10, 2002 BACKGROUND: During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and a ... Cite

The cxc chemokine cCAF stimulates differentiation of fibroblasts into myofibroblasts and accelerates wound closure.

Journal Article J Cell Biol · January 7, 2002 Featured Publication Chemokines are small cytokines primarily known for their roles in inflammation. More recently, however, they have been implicated in processes involved in development of the granulation tissue of wounds, but little is known about their functions during thi ... Full text Link to item Cite

Novel nuclear target for thrombin: activation of the Elk1 transcription factor leads to chemokine gene expression.

Journal Article Blood · December 1, 2000 Featured Publication Thrombin is primarily known for its role in homeostasis and thrombosis. However, this enzyme also plays important roles in wound healing and pathologic situations such as inflammation and tumorigenesis. Among the molecules stimulated by thrombin in these l ... Link to item Cite

Isolation and characterization of a new chemokine receptor gene, the putative chicken CXCR1.

Journal Article Gene · October 31, 2000 This study delineates the isolation and characterization of a novel chemokine receptor gene, the putative chicken CXC receptor 1 (cCXCR1). Using a human CXCR1 probe, we isolated several positive clones from a chicken genomic library. One of the clones cont ... Full text Link to item Cite

Activation of the 9E3/cCAF chemokine by phorbol esters occurs via multiple signal transduction pathways that converge to MEK1/ERK2 and activate the Elk1 transcription factor.

Journal Article J Biol Chem · May 28, 1999 Featured Publication Using primary fibroblasts in culture, we have investigated the signal transduction mechanisms by which phorbol esters, a class of tumor promoters, activate the 9E3 gene and its chemokine product the chicken chemotactic and angiogenic factor. This gene is h ... Full text Link to item Cite

Management of residual cancer tissue on cutting surface with ethanal during hepatectomy

Journal Article Chinese Journal of Clinical Oncology · January 1, 1995 Due to the fact that primary liver cancer possesses no capsule in addition to many of the following features such as infiltrative growth, ill-defined border, associated with liver cirrhosis, cutting surface with residue of carcinoma during hepatectomy is v ... Cite