干细胞样 CD8 T 细胞 (TSL) 是免疫细胞的一个子集，具有卓越的持久性和抗肿瘤免疫力。它们是 TCF1 PD-1，对于响应检查点阻断免疫疗法而扩增肿瘤特异性 CD8 T 细胞非常重要。在急性感染中，幼稚 CD8 T 细胞分化为效应 CD8 T 细胞和记忆 CD8 T 细胞；在癌症和慢性感染中，持续的抗原刺激会导致 T 细胞耗竭。最近的研究强调了晚期功能障碍（或耗尽）T 细胞（TLD）（即 TCF1-PD-1）和其来源的自我更新 TCF1 PD-1 TSL 之间的二分法。 TCF1 TSL 细胞被认为具有类似于记忆 T 细胞群的干细胞样特性，可以产生细胞毒性效应子和介导肿瘤控制的瞬时 T 细胞表型 (TTE)。在这篇综述中，我们将讨论 TSL 形成和扩展研究的最新进展，以及它们在癌症环境中分化和维持所需的独特生态位。我们还将讨论生成这些细胞的潜在策略，以及对疫苗设计、免疫检查点封锁 (ICB) 和过继性 T 细胞疗法中干性增强的临床意义。版权所有 © 2024 Steiner、Denlinger、Huang 和 Yang。

Stem-like CD8+ T cells (TSL) are a subset of immune cells with superior persistence and antitumor immunity. They are TCF1+ PD-1+ and important for the expansion of tumor specific CD8+ T cells in response to checkpoint blockade immunotherapy. In acute infections, naïve CD8+ T cells differentiate into effector and memory CD8+ T cells; in cancer and chronic infections, persistent antigen stimulation can lead to T cell exhaustion. Recent studies have highlighted the dichotomy between late dysfunctional (or exhausted) T cells (TLD) that are TCF1- PD-1+ and self-renewing TCF1+ PD-1+ TSL from which they derive. TCF1+ TSL cells are considered to have stem cell-like properties akin to memory T cell populations and can give rise to cytotoxic effector and transitory T cell phenotypes (TTE) which mediate tumor control. In this review, we will discuss recent advances made in research on the formation and expansion of TSL, as well as distinct niches required for their differentiation and maintenance in the setting of cancer. We will also discuss potential strategies to generate these cells, with clinical implications for stemness enhancement in vaccine design, immune checkpoint blockade (ICB), and adoptive T cell therapies.Copyright © 2024 Steiner, Denlinger, Huang and Yang.