Stampouloglou, EleniCheng, NanFederico, AnthonySlaby, EmilyMonti, StefanoSzeto, Gregory L.Varelas, Xaralabos2020-07-282020-07-282020-01-13: Stampouloglou E, Cheng N, Federico A, Slaby E, Monti S, Szeto GL, et al. (2020) Yap suppresses T-cell function and infiltration in the tumor microenvironment. PLoS Biol 18(1): e3000591. https://doi.org/10.1371/journal. pbio.3000591https://doi.org/10.1371/journal.pbio.3000591http://hdl.handle.net/11603/19263A major challenge for cancer immunotherapy is sustaining T-cell activation and recruitment in immunosuppressive solid tumors. Here, we report that the levels of the Hippo pathway effector Yes-associated protein (Yap) are sharply induced upon the activation of cluster of differentiation 4 (CD4)-positive and cluster of differentiation 8 (CD8)-positive 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 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 Yap inhibition improves T-cell responses in cancer.27 pagesen-USThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.Attribution 4.0 InternationalUMBC High Performance Computing Facility (HPCF)Text