在持续接触抗原的情况下，例如慢性感染或癌症，抗原特异性 CD8 T 细胞可能会出现功能障碍或耗尽。这种变化的标志是抑制性受体（PD-1 和 Tim-3）表达水平的增加。干细胞耗竭型祖细胞 (Tpex) 是表达 TCF-1 的耗竭细胞的一个子集，主要存在于淋巴结中，具有自我更新的能力并表现出高增殖率。 Tpex细胞可以进一步分化为过渡中间耗尽（Tex-int）细胞和终末耗尽（Tex-term）细胞。或者，它们可以直接分化为 Tex-term 细胞。 Tpex 细胞是对免疫检查点抑制剂 (ICI) 产生反应的主要细胞亚群，使其成为提高 ICI 疗法疗效的主要候选细胞。本文旨在介绍癌症背景下 Tpex 形成、扩增和分化领域的最新进展，以及它们对癌症免疫治疗中 ICI 的反应。因此，有可能开发出专门针对 Tpex 细胞的新疗法，从而改善整体治疗结果。要点：Tpex 细胞位于淋巴结和 TLS。多种途径控制 Tpex 细胞的分化轨迹，包括表观遗传因子、转录因子、细胞因子、年龄、性别等。© 2024 作者。约翰·威利出版的《临床与转化医学》

In situations involving continuous exposure to antigens, such as chronic infections or cancer, antigen-specific CD8+ T cells can become dysfunctional or exhausted. This change is marked by increased expression levels of inhibitory receptors (PD-1 and Tim-3). Stem-like progenitor exhausted (Tpex) cells, a subset of exhausted cells that express TCF-1 and are mainly found in the lymph nodes, demonstrate the ability to self-renew and exhibit a high rate of proliferation. Tpex cells can further differentiate into transitional intermediate exhausted (Tex-int) cells and terminally exhausted (Tex-term) cells. Alternatively, they can directly differentiate into Tex-term cells. Tpex cells are the predominant subset that respond to immune checkpoint inhibitors (ICI), making them a prime candidate for improving the efficacy of ICI therapy. This review article aimed to present the latest developments in the field of Tpex formation, expansion, and differentiation in the context of cancer, as well as their responses to ICIs in cancer immunotherapy. Consequently, it may be possible to develop novel treatments that exclusively target Tpex cells, thus improving overall treatment outcomes. KEY POINTS: Tpex cells are located in lymph nodes and TLS. Several pathways control the differentiation trajectories of Tpex cells, including epigenetic factors, transcription factors, cytokines, age, sex, etc.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.