CAR-T细胞治疗肿瘤中T细胞耗竭现象的作用机制和策略  

Mechanism and Strategy of CAR-T Cell Therapy for T Cell Exhaustion in Tumor

作　　者：莫馨霈 李艳 段勇[1,2,3] 熊秋霞 Mo Xinpei;Li Yan;Duan Yong(Yunnan Key Laboratory of Laboratory Medicine;Clinical Research Center of Laboratory Medicine of Yunnan Province;Clinical Laboratory and Diagnostic Innovation Team,The First Affiliated Hospital of Kunming Medical University,Kunming 650032,China)

机构地区：[1]云南检验医学重点实验室 [2]中国云南省检验医学临床研究中心 [3]昆明医科大学第一附属医院临床实验室与诊断创新团队,昆明650032

出　　处：《华中科技大学学报（医学版）》2024年第5期705-712,共8页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.82060515,No.82160407)。

摘　　要：嵌合抗原受体T细胞(CAR-T)免疫疗法以T细胞为来源,通过体外基因修饰后回输治疗,被广泛应用于不同疾病,尤其是血液病的治疗。尽管CAR-T细胞具有许多优点,如治疗效果显著,但也面临一些挑战:副作用和毒性、CAR-T细胞耗竭、肿瘤微环境的免疫抑制状态和基因改变等。CAR-T细胞在实体瘤治疗中的临床效果受到限制,且患者常出现复发。CAR-T细胞耗竭一直是难以解决的问题。为提高CAR-T疗法的可靠性和实用性,科学家正在采取多种技术手段来抑制CAR-T细胞耗竭的发生。该文探讨了T细胞耗竭和CAR-T细胞耗竭的机制,以及减轻或中断CAR-T细胞耗竭的策略,综述CAR-T细胞耗竭的研究进展,旨在寻找逆转CAR-T细胞功能的最佳策略,为CAR-T治疗技术的改进提供更全面的理论依据。CAR-T cell immunotherapy,which is derived from T cells and employed in various diseases,particularly blood disorders,involves in vitro gene modification and infusion for treatment.Despite the significant therapeutic effects of CAR-T cells,challenges such as side effects,toxicity,CAR-T cell exhaustion,the immunosuppressive tumor microenvironment,and genetic alterations exist.The clinical efficacy of CAR-T cells in solid tumor treatment is limited,often leading to patient relapse.Addressing CAR-T-cell exhaustion remains a significant challenge.Scientists are employing diverse technical approaches to prevent CAR-T-cell exhaustion to increase the reliability and utility of CAR-T-cell therapy.This article delves into the mechanisms of T-cell depletion and CAR-T-cell exhaustion,along with strategies to alleviate or disrupt CAR-T-cell exhaustion.This review of research progress on CAR-T-cell exhaustion aims to identify optimal strategies for reversing CAR-T-cell function and provide a comprehensive theoretical foundation for enhancing CAR-T-cell therapy technology.

关 键 词：嵌合抗原受体T细胞 T细胞耗竭 癌症 免疫疗法 

分 类 号：R730.51[医药卫生—肿瘤]