卵巢癌是常见的妇科恶性肿瘤，其治疗仍具有挑战性。尽管卵巢癌可能因分子或T细胞水平上的内源性免疫而对免疫治疗产生反应，但免疫治疗迄今为止尚未达到预期效果。预先存在的T细胞的功能状态是强大的抗肿瘤免疫力和免疫治疗不可或缺的决定因素。 T 细胞耗竭和衰老是 T 细胞功能障碍的两种关键状态，它们具有一些重叠的表型和功能特征，但每种状态都具有独特的分子和发育特征。人们普遍认为，T细胞的耗竭和衰老是癌细胞逃避免疫监视和维持免疫抑制微环境的重要策略。在此，本综述总结了耗尽和衰老T细胞的表型和功能特征，并描述了肿瘤微环境中两种T细胞功能障碍状态的关键驱动因素及其在卵巢癌中的功能作用。此外，我们总结了控制 T 细胞耗竭和衰老的分子机制和信号通路。还探索了可以预防和/或逆转 T 细胞功能障碍的可能策略。对衰竭和衰老 T 细胞的深入了解将提供新的策略，通过将肿瘤特异性 T 细胞重新定向，使其远离功能失调的发育轨迹，从而增强卵巢癌的免疫治疗。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Ovarian cancer is a common gynecological malignancy, and its treatment remains challenging. Although ovarian cancer may respond to immunotherapy because of endogenous immunity at the molecular or T cell level, immunotherapy has so far not had the desired effect. The functional status of preexisting T cells is an indispensable determinant of powerful antitumor immunity and immunotherapy. T cell exhaustion and senescence are two crucial states of T cell dysfunction, which share some overlapping phenotypic and functional features, but each status possesses unique molecular and developmental signatures. It has been widely accepted that exhaustion and senescence of T cells are important strategies for cancer cells to evade immunosurveillance and maintain the immunosuppressive microenvironment. Herein, this review summarizes the phenotypic and functional features of exhaust and senescent T cells, and describes the key drivers of the two T cell dysfunctional states in the tumor microenvironment and their functional roles in ovarian cancer. Furthermore, we present a summary of the molecular machinery and signaling pathways governing T cell exhaustion and senescence. Possible strategies that can prevent and/or reverse T cell dysfunction are also explored. An in-depth understanding of exhausted and senescent T cells will provide novel strategies to enhance immunotherapy of ovarian cancer through redirecting tumor-specific T cells away from a dysfunctional developmental trajectory.Copyright © 2024 Elsevier Ltd. All rights reserved.