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.

中文翻译：

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Yap抑制肿瘤微环境中的T细胞功能和浸润。

癌症免疫疗法的主要挑战是在免疫抑制性实体瘤中维持T细胞活化和募集。在这里，我们报告说，激活分化4（CD4）阳性簇和分化8（CD8）阳性T细胞簇以及Yap时，河马途径效应物Yes相关蛋白（Yap）的水平被强烈诱导。用作免疫抑制因子和效应分化的抑制剂。T细胞中Yap的丧失导致增强的T细胞活化，分化和功能，这在体内转化为T细胞浸润和抑制肿瘤的能力增强。Yap缺失后肿瘤浸润性T细胞的基因表达分析表明Yap在肿瘤微环境中是整体T细胞反应的介体，并且是多种人类癌症中T细胞肿瘤浸润和患者生存的负调节剂。总的来说，我们的结果表明Yap在T细胞生物学中起关键作用，并表明Yap抑制可改善癌症中的T细胞反应。