Yap suppresses T-cell function and infiltration in the tumor microenvironment

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

[thumbnail of file_id=10.1371%2Fjournal.pbio.3000591&type=printable] Text
file_id=10.1371%2Fjournal.pbio.3000591&type=printable - Published Version

Download (3MB)

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
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

Actions (login required)

View Item
View Item