Institute for Immunology and School of Basic Medicine, Tsinghua University, Beijing, China.
Clin Transl Med. 2024 Aug;14(8):e1817. doi: 10.1002/ctm2.1817.
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.
在持续暴露于抗原的情况下，如慢性感染或癌症，抗原特异性 CD8 T 细胞可能会变得功能失调或耗竭。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。干细胞样祖细胞耗竭（Tpex）细胞是耗尽细胞的一个子集，表达 TCF-1，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性中间耗竭（Tex-int）细胞和终末耗竭（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）有反应的主要亚群，使其成为提高 ICI 治疗效果的首选候选者。这篇综述文章旨在介绍癌症中 Tpex 形成、扩增和分化的最新进展，以及它们在癌症免疫治疗中对 ICIs 的反应。因此，有可能开发专门针对 Tpex 细胞的新型治疗方法，从而提高整体治疗效果。要点：Tpex 细胞位于淋巴结和 TLS 中。有几种途径控制 Tpex 细胞的分化轨迹，包括表观遗传因素、转录因子、细胞因子、年龄、性别等。
