肿瘤特异性CD8+T细胞研究现状

CD8⁺ T细胞是介导抗原特异性免疫应答的主要细胞，其功能状态受到分子机制的精密调控，在肿瘤免疫中发挥关键作用。近年来，基于CD8⁺ T细胞杀伤功能的过继性细胞疗法 （例如TCR-T和CAR-T细胞治疗） 和阻断PD-1抑制性信号的免疫检测点疗法在肿瘤临床治疗中取得了前所未有的效果。但是这些免疫疗法对患者的治疗效果仍然有限，主要表现为免疫治疗抵抗，其中重要的机制是肿瘤抗原特异性CD8⁺ T细胞功能耗竭。因此，免疫治疗研究的热点和难点是探究肿瘤抗原特异性CD8⁺ T细胞功能耗竭的调控机制，并探索干预策略和靶点以增强CD8⁺ T细胞的效应功能，抵抗功能耗竭。本文分别从耗竭 CD8⁺ T 细胞的异质性、对 PD-1 ICB 的响应及表观遗传特征三个方面综述 CD8⁺ T 细胞抗肿瘤免疫应答的研究进展。

Insights into antigen specific CD8+ T cell exhaustion

CD8⁺ T cells are the primary mediators of antigen-specific immune responses, with their functional states finely regulated by molecular mechanisms, playing a crucial role in tumor immunity. In recent years, CD8⁺ T-cell-based cellular therapies (e.g., TCR-T and CAR-T cell therapy) and immune checkpoint therapies that block PD-1 signaling pathway have achieved unprecedented success in clinical cancer treatments. However, the therapeutic effects of these immunotherapies are still limited, mainly due to immune resistance, with a significant factor being the functional exhaustion of tumor antigen-specific CD8⁺ T cells. Consequently, a major focus and challenge in immunotherapy research is to understand the regulatory mechanisms behind this functional exhaustion and to develop intervention strategies and targets to enhance CD8⁺ T cell effector functions. This article reviews the research progress in antitumor immune responses of CD8⁺ T cells from three perspectives: The heterogeneity of exhausted CD8⁺ T cells, their response to PD-1 immune checkpoint blockade (ICB), and their epigenetic characteristics.