Yap suppresses T-cell function and infiltration in the tumor microenvironment.
PLoS Biol
; 18(1): e3000591, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31929526
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Quimiotaxia de Leucócito
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Proteínas de Ciclo Celular
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Proteínas Adaptadoras de Transdução de Sinal
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Microambiente Tumoral
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article