First Author | Stampouloglou E | Year | 2020 |
Journal | PLoS Biol | Volume | 18 |
Issue | 1 | Pages | e3000591 |
PubMed ID | 31929526 | Mgi Jnum | J:284070 |
Mgi Id | MGI:6389217 | Doi | 10.1371/journal.pbio.3000591 |
Citation | Stampouloglou E, et al. (2020) Yap suppresses T-cell function and infiltration in the tumor microenvironment. PLoS Biol 18(1):e3000591 |
abstractText | A 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. |