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You-Wen He

Professor of Integrative Immunobiology
Integrative Immunobiology
Box 3010 DUMC, 335 Jones Building, Durham, NC 27710
335 Jones Building, 207 Resear, Box 3010 DUMC, Durham, NC 27710

Overview


We study T cell biology in health and disease. Our current study is divided into two parts. Part I is to investigate T lymphocyte-mediated anti-caner immunity. We have found that host complement inhibits the cytokine IL-10 production in CD8+ tumor infiltrating lymphocytes through complement receptors C3aR and C5aR. Complement-deficient animals are resistant to tumor development in a T cell- and IL-10-dependent manner. CD8+ tumor infiltrating T cells express IL-10 when complement signaling is disabled. We found that tumor infiltrating lymphocytes from human cancers expanded with IL-2 plus IL-10 are potent tumor killers. Complement-mediated inhibition on antitumor immunity is independent of the PD-1/PD-L1 immune checkpoint pathway. Our findings suggest that complement receptors C3aR and C5aR expressed on CD8+ tumor infiltrating lymphocytes represent a novel class of immune checkpoints that needs to be targeted for tumor immunotherapy. Our current effort is to enhance cancer immunotherapy through several strategies. First, we investigate a combined blockade of complement signaling and anti-PD-1 to enhance the antitumor efficacy; second, we are studying the antitumor efficacy of a targeted delivery of IL-10 to antitumor CD8+ T cells by using anti-PD1-IL-10 or anti-CTLA-4-IL-10 fusion proteins; third, we are studying the tumor killing efficacy of addition of IL-10 in the expansion protocol of tumor infiltrating lymphocytes for adaptive cellular therapy.

Part II is to investigate the intracellular process termed autophagy in T lymphocyte function. Autophagy is a highly conserved self-digestion pathway that plays essential roles in maintaining the homeostasis of organelles, degrading long-lived proteins and recycling amino acids under starvation conditions. We have found that autophagy related molecules are expressed in T lymphocytes and autophagy occurs inside T lymphocytes. We have generated autophagy-deficient T lymphocytes in multiple genetic models and investigated the roles of autophagy in T lymphocytes. We found that autophagy plays a critical role in T lymphocyte function. Our current effort is to elucidate the molecular pathways by which TCR signal induces autophagy and the impact of autophagy on intracellular organelle homeostasis in dividing T cells.   

Current Appointments & Affiliations


Professor of Integrative Immunobiology · 2013 - Present Integrative Immunobiology, Basic Science Departments
Member of the Duke Cancer Institute · 2000 - Present Duke Cancer Institute, Institutes and Centers

Recent Publications


Identification of growth differentiation factor 15 as an early predictive biomarker for metabolic dysfunction-associated steatohepatitis: A nested case-control study of UK Biobank proteomic data.

Journal Article Diabetes Obes Metab · May 2025 AIMS: This study aims to determine the predictive capability for metabolic dysfunction-associated steatohepatitis (MASH) long before its diagnosis by using six previously identified diagnostic biomarkers for metabolic dysfunction-associated steatotic liver ... Full text Link to item Cite

Association of pre-diagnosis plasma proteomic contexture with overall survival of early- and late-stage colon cancer patients.

Journal Article BMC Cancer · April 21, 2025 BACKGROUND: The pre-diagnosis plasma proteomic contexture of colon cancer patients may reflect host immune and biological conditions and potentially associate with survival outcomes. We aimed to characterize pre-diagnosis proteomic contextures in colon can ... Full text Link to item Cite

Vps34 puts the 'e' in eTreg cells.

Journal Article PLoS Biol · April 2025 Regulatory T cells (Tregs) exist in distinct subsets, but key regulators of their heterogeneity remain unclear. A recent PLOS Biology study shows that the class III PI3K Vps34 acts as a master orchestrator, driving effector Treg generation and maintenance. ... Full text Link to item Cite
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Recent Grants


Medical Scientist Training Program

Inst. Training Prgm or CMEPreceptor · Awarded by National Institute of General Medical Sciences · 2022 - 2027

Basic Immunology Training Program

Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2020 - 2025

The Effect of a Desensitization Protocol in Highly Sensitized Renal Transplant Recipients on T Follicular Helper Cells

FellowshipCollaborator · Awarded by National Institutes of Health · 2023 - 2024

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Education, Training & Certifications


University of Miami · 1996 Ph.D.
Fourth Military Medical University (China) · 1986 M.D.