摘要
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.
作者
朱元玲
王月丹
李海潮
ZHU Yuan-Ling;WANG Yue-Dan;LI Hai-Chao(Department of Respiratory and Critical Care Medicine,Peking University First Hospital,Beijing 100034,China;Department of Immunology,School of Basic Medical Science,Peking University,Beijing 100191,China)
出处
《生理科学进展》
CAS
北大核心
2024年第6期499-506,共8页
Progress in Physiological Sciences
基金
科技部国家重点研发计划“战略性科技创新合作”重点专项(SQ2021YFE020462)
香港创新科技署内地与香港联合资助计划项目(MHX/123/21)资助课题。
