肿瘤免疫治疗在临床中取得了良好的治疗效果,受到越来越多的关注。其中嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞在血液系统肿瘤中的治疗更是取得了突破性进展。然而,随着肿瘤抗原的长期刺激,CAR-T细胞在体内会出现耗竭现象。CAR-T细胞的耗竭会导致治疗效果不佳或治疗后肿瘤复发。其耗竭的机制涉及耗竭相关转录因子的表达、肿瘤免疫抑制性微环境的作用以及CAR结构本身的影响等一系列过程。本文旨在总结CAR-T 细胞耗竭的过程 和机制,以及通过改善T细胞耗竭来提高CAR-T细胞治疗效果的可能途径,以期促进CAR-T 治疗在肿瘤治疗中的应用。

Tumor immunotherapy has achieved impressive therapeutic effects in clinical practice and has attracted increasing attention. Among them, chimeric antigen receptor T (CAR-T) cell therapy has made breakthrough progress in the treatment of hematological malignancies. However, with prolonged exposure to tumor antigens, CAR-T cells may become exhausted in vivo. The exhaustion of CAR-T cells can lead to poor treatment efficacy or tumor recurrence. The mechanism of CAR-T cell exhaustion involves a series of processes, such as the expression of exhaustion-associated transcription factors, the role of the immunosuppressive tumor microenvironment, and the influence of CAR structure itself. Here, we summarize the process and underlying mechanisms of CAR-T cell exhaustion, as well as potential solutions to improve T cell exhaustion and enhance the efficacy of CAR-T cell therapy, with the aim of expanding the application of CAR-T cell therapy in tumor treatment.