Yap suppresses T cell function and infiltration in the tumor microenvironment

Eleni Stampouloglou, Anthony Federico, Emily Slaby, Stefano Monti, Gregory L. Szeto, Xaralabos Varelas
2019 · doi:10.1101/644757
preprint OA: closed CC-BY-NC-ND-4.0
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Abstract

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.

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License: CC-BY-NC-ND-4.0