生理科学进展2024,Vol.55Issue(6) :499-506.DOI:10.20059/j.cnki.pps.2024.04.1007

CAR-T细胞治疗中T细胞的耗竭及改善途径

T Cell Exhaustion in CAR-T Cell Therapy:Mechanisms and Potential Solutions

朱元玲 王月丹 李海潮
生理科学进展2024,Vol.55Issue(6) :499-506.DOI:10.20059/j.cnki.pps.2024.04.1007

CAR-T细胞治疗中T细胞的耗竭及改善途径

T Cell Exhaustion in CAR-T Cell Therapy:Mechanisms and Potential Solutions

朱元玲 1王月丹 2李海潮1
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作者信息

  • 1. 北京大学第一医院呼吸与危重症医学科,北京 100034
  • 2. 北京大学基础医学院免疫学系,北京 100191
  • 折叠

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.

Abstract

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.Howev-er,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 mecha-nism of CAR-T cell exhaustion involves a series of processes,such as the expression of exhaus-tion-associated transcription factors,the role of the immunosuppressive tumor microenviron-ment,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.

关键词

CAR-T细胞/T细胞耗竭/免疫治疗/肿瘤

Key words

CAR-T cells/T cell exhaustion/immunotherapy/tumor

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出版年

2024
生理科学进展
中国生理学会,北京大学

生理科学进展

CSTPCD北大核心
影响因子:0.635
ISSN:0559-7765
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