Stampouloglou, Eleni and Cheng, Nan and Federico, Anthony and Slaby, Emily and Monti, Stefano and Szeto, Gregory L. and Varelas, Xaralabos and Bhandoola, Avinash (2020) Yap suppresses T-cell function and infiltration in the tumor microenvironment. PLOS Biology, 18 (1). e3000591. ISSN 1545-7885
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Abstract
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.
Item Type: | Article |
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Subjects: | Journal Eprints > Biological Science |
Depositing User: | Managing Editor |
Date Deposited: | 28 Jan 2023 06:49 |
Last Modified: | 05 Jul 2024 09:13 |
URI: | http://repository.journal4submission.com/id/eprint/1134 |