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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.
Research Interests
Papers共 203 篇Author StatisticsCo-AuthorSimilar Experts
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Research Square (Research Square)no. 10 (2024): 1589-1601
EBioMedicine (2024): 105186
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FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2024): 1302490-1302490
eBioMedicine (2024): 105186-105186
Research Square (Research Square) (2023)
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESno. 24 (2023): 17319
Journal of Pharmaceutical Analysisno. 6 (2023): 616-624
Breast Cancer Research and Treatmentno. 1 (2023): 1-17
Molecular cancer therapeuticsno. 6 (2023): 778-789
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#Papers: 203
#Citation: 12554
H-Index: 62
G-Index: 109
Sociability: 7
Diversity: 0
Activity: 1
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