Skip to main content

You-Wen He, MD, PhD

Professor of Immunology
Campus Mail: 335 Jones Building, 207 Resear, Box 3010 DUMC, Durham, NC 27710
Phone: (919) 613-7870
Email: he000004@mc.duke.edu

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.   

 

 

 

Education and Training

  • Senior Fellow, Immunology, University of Washington, 1996 - 2000
  • Ph.D., University of Miami, 1996
  • M.D., Fourth Military Medical University (China), 1986

Selected Publications

Lu, Ligong, Jun Jiang, Meixiao Zhan, Hui Zhang, Qian-Ting Wang, Sheng-Nan Sun, Xiao-Kai Guo, et al. “Targeting Tumor-Associated Antigens in Hepatocellular Carcinoma for Immunotherapy: Past Pitfalls and Future Strategies.” Hepatology 73, no. 2 (February 2021): 821–32. https://doi.org/10.1002/hep.31502.

Full Text

Lu, Ligong, Jun Jiang, Meixiao Zhan, Hui Zhang, Qian-Ting Wang, Sheng-Nan Sun, Xiao-Kai Guo, et al. “Targeting Neoantigens in Hepatocellular Carcinoma for Immunotherapy: A Futile Strategy?” Hepatology 73, no. 1 (January 2021): 414–21. https://doi.org/10.1002/hep.31279.

Full Text

Lu, Ligong, Hui Zhang, Meixiao Zhan, Jun Jiang, Hua Yin, Danielle J. Dauphars, Shi-You Li, Yong Li, and You-Wen He. “Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?” Sci China Life Sci 63, no. 12 (December 2020): 1833–49. https://doi.org/10.1007/s11427-020-1859-y.

Full Text

Wang, Qian-Ting, Ying Nie, Sheng-Nan Sun, Tao Lin, Ru-Jin Han, Jun Jiang, Zhe Li, et al. “Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients.” Cancer Immunol Immunother 69, no. 7 (July 2020): 1375–87. https://doi.org/10.1007/s00262-020-02496-w.

Full Text

Zhang, Hui, Yu Wang, Qian-Ting Wang, Sheng-Nan Sun, Shi-You Li, Hong Shang, and You-Wen He. “Enhanced Human T Lymphocyte Antigen Priming by Cytokine-Matured Dendritic Cells Overexpressing Bcl-2 and IL-12.” Front Cell Dev Biol 8 (2020): 205. https://doi.org/10.3389/fcell.2020.00205.

Full Text

Lu, Ligong, Hui Zhang, Meixiao Zhan, Jun Jiang, Hua Yin, Danielle J. Dauphars, Shi-You Li, Yong Li, and You-Wen He. “Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?” Front Cell Dev Biol 8 (2020): 677. https://doi.org/10.3389/fcell.2020.00677.

Full Text

Li, Jun-Qi, Qian-Ting Wang, Ying Nie, Yun-Peng Xiao, Tao Lin, Ru-Jin Han, Zhe Li, et al. “A Multi-Element Expression Score Is A Prognostic Factor In Glioblastoma Multiforme.” Cancer Manag Res 11 (2019): 8977–89. https://doi.org/10.2147/CMAR.S228174.

Full Text

Csepregi, Janka Zsófia, Anita Orosz, Erik Zajta, Orsolya Kása, Tamás Németh, Edina Simon, Szabina Fodor, et al. “Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form.” J Immunol 201, no. 12 (December 15, 2018): 3793–3803. https://doi.org/10.4049/jimmunol.1701803.

Full Text

Csepregi, J. Z., E. Zajta, K. Csonka, Y. -. W. He, A. Gacser, and A. Mocsai. “The Mcl-1 Delta Myelo mice are highly susceptible to microbial infections.” In European Journal of Clinical Investigation, 47:145–145. WILEY, 2017.

Scholars@Duke

Wang, Yu, Sheng-Nan Sun, Qing Liu, Yang-Yang Yu, Jian Guo, Kun Wang, Bao-Cai Xing, et al. “Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression.” Cancer Discov 6, no. 9 (September 2016): 1022–35. https://doi.org/10.1158/2159-8290.CD-15-1412.

Full Text

Scherr, Anna-Lena, Georg Gdynia, Mariam Salou, Praveen Radhakrishnan, Katarina Duglova, Anette Heller, Sophia Keim, et al. “Bcl-xL is an oncogenic driver in colorectal cancer.” Cell Death Dis 7, no. 8 (August 18, 2016): e2342. https://doi.org/10.1038/cddis.2016.233.

Full Text

Wu, Yu-Jung, Yung-Hsuan Wu, Shu-Ting Mo, Huey-Wen Hsiao, You-Wen He, and Ming-Zong Lai. “Cellular FLIP Inhibits Myeloid Cell Activation by Suppressing Selective Innate Signaling.” J Immunol 195, no. 6 (September 15, 2015): 2612–23. https://doi.org/10.4049/jimmunol.1402944.

Full Text

Pages