RT Journal Article
SR Electronic
T1 Yap suppresses T cell function and infiltration in the tumor microenvironment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 644757
DO 10.1101/644757
A1 Eleni Stampouloglou
A1 Anthony Federico
A1 Emily Slaby
A1 Stefano Monti
A1 Gregory L. Szeto
A1 Xaralabos Varelas
YR 2019
UL http://biorxiv.org/content/early/2019/05/21/644757.abstract
AB 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 CD4+ and CD8+ T cell activation and that Yap functions as an immunosuppressive factor and inhibitor of effector differentiation. Loss of Yap 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.