Yap suppresses T cell function and infiltration in the tumor microenvironment
Yap suppresses T cell function and infiltration in the tumor microenvironment
ABSTRACT A major challenge for cancer immunotherapy is sustaining T cell activation and recruitment in immunosuppressive solid tumors. Here we report that Yap levels are sharply induced upon activation of CD4+ and CD8+ T cells and that Yap functions as an immunosuppressive factor and inhibitor of effector differentiation. Loss of Yap in T cells results in enhanced T cell activation, differentiation and function, which translates in vivo to an improved ability for T cells to infiltrate and repress tumors. Gene expression analyses of tumor-infiltrating T cells following Yap deletion implicates Yap as a mediator of global T cell responses in the tumor microenvironment and as a key negative regulator of T cell tumor infiltration and patient survival in diverse human cancers. Collectively, our results indicate that Yap plays critical roles in T cell biology, and suggest that inhibiting Yap activity improves T cell responses in cancer.
Varelas Xaralabos、Stampouloglou Eleni、Monti Stefano、Slaby Emily、Federico Anthony、Szeto Gregory L.
Department of Biochemistry, Boston University School of MedicineDepartment of Biochemistry, Boston University School of MedicineDepartment of Medicine, Division of Computational Biology, Boston University School of Medicine||Bioinformatics Program, Boston UniversityDepartment of Chemical, Biochemical, and Environmental Engineering, University of Maryland Baltimore CountyDepartment of Medicine, Division of Computational Biology, Boston University School of Medicine||Bioinformatics Program, Boston UniversityDepartment of Chemical, Biochemical, and Environmental Engineering, University of Maryland Baltimore County||Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland
肿瘤学基础医学
Varelas Xaralabos,Stampouloglou Eleni,Monti Stefano,Slaby Emily,Federico Anthony,Szeto Gregory L..Yap suppresses T cell function and infiltration in the tumor microenvironment[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/644757.点此复制
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