The functional state of the preexisting T cells in the tumor microenvironment is a key determinant for effective antitumor immunity and immunotherapy. Increasing evidence suggests that immunosenescence is an important state of T cell dysfunction that is distinct from exhaustion, a key strategy used by malignant tumors to evade immune surveillance and sustain the suppressive tumor microenvironment. Here, we discuss the phenotypic and functional characteristics of senescent T cells and their role in human cancers. We also explore the possible mechanisms and signaling pathways responsible for induction of T cell senescence by malignant tumors, and then discuss potential strategies to prevent and/or reverse senescence in tumor-specific T cells. A better understanding of these critical issues should provide novel strategies to enhance cancer immunotherapy.

中文翻译：

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抑制性肿瘤微环境中的衰老 T 细胞：肿瘤免疫治疗的新兴靶点。

肿瘤微环境中预先存在的 T 细胞的功能状态是有效抗肿瘤免疫和免疫治疗的关键决定因素。越来越多的证据表明，免疫衰老是 T 细胞功能障碍的一种重要状态，不同于衰竭，这是恶性肿瘤用来逃避免疫监视和维持抑制性肿瘤微环境的关键策略。在这里，我们讨论衰老 T 细胞的表型和功能特征及其在人类癌症中的作用。我们还探讨了恶性肿瘤诱导 T 细胞衰老的可能机制和信号通路，然后讨论了预防和/或逆转肿瘤特异性 T 细胞衰老的潜在策略。