耗竭CD8^(+)T细胞分化调控与亚群分型的研究进展  

Progress in differentiation regulation and subpopulation typing of exhausted CD8^(+)T cells

作　　者：曹振楠 陈刚 邓彬[1] Cao Zhennan;Chen Gang;Deng Bin(Department of Gastroenterology,the Affiliated Hospital of Yangzhou University,Yangzhou 225001,China;School of Rehabilitation Science and Engineering,University of Health and Rehabilitation Sciences,Qingdao 266024,China)

机构地区：[1]扬州大学附属医院消化内科,扬州225001 [2]康复大学(筹)康复科学与工程学院,青岛266024

出　　处：《中华微生物学和免疫学杂志》2022年第11期899-905,共7页Chinese Journal of Microbiology and Immunology

基　　金：江苏省卫健委重点项目(ZD2021038);扬州市社会发展项目(YZ2020069)。

摘　　要：耗竭CD8^(+)T细胞(exhausted CD8^(+)T cells,CD8^(+)Tex)是一种由静止CD8^(+)T细胞在持续高抗原刺激条件下形成的独特亚群。静息CD8^(+)T细胞在短期抗原刺激下可分化为具有细胞毒性的功能细胞并发挥抗感染和抗肿瘤作用,而持续的高抗原刺激将使效应CD8^(+)T细胞逐渐分化为终末CD8^(+)Tex细胞并且不可逆转地失去效应器功能。与记忆和效应T细胞不同,CD8^(+)Tex细胞具有一个独特的转录程序。同时,众多研究正在试图绘制一个详尽的CD8^(+)Tex亚型分化图谱,旨在未来通过靶向CD8^(+)Tex细胞内的单个亚群或单个分化阶段来最大限度增加效应T细胞的数量,同时避免损伤效应细胞。本文结合最新研究进展,从转录失调、代谢重编、亚群分型及临床应用等方面进行综述,旨在为以CD8^(+)T细胞为基础的肿瘤免疫学疗法提供更多治疗策略。Exhausted CD8^(+)T cells(CD8^(+)Tex)are a distinct subpopulation formed from naive CD8^(+)T cells under conditions of sustained high antigen stimulation.Initially,naive CD8^(+)T cells can differentiate into functional cytotoxic cells and exert anti-infective and anti-tumor effects upon short-term antigen stimulation.However,sustained high antigen stimulation will make effector CD8^(+)T cells progressively differentiate into terminally CD8^(+)Tex cells and irreversibly lose effector function.Unlike memory and effector T cells,CD8^(+)Tex cells have a unique transcriptional program.Numerous studies are attempting to map a detailed differentiation landscape of CD8^(+)Tex cell subsets,aiming to maximize the number of effector T cells in the future by targeting individual subsets or individual differentiation stages in CD8^(+)Tex cells without damaging the effector cells.This article reviewed the progress in CD8^(+)Tex cells from the aspects of transcriptional dysregulation,metabolic reprogramming,subpopulation typing and clinical application,aiming to provide more CD8^(+)T cell-based therapeutic strategies for tumor.

关 键 词：耗竭CD8^(+)T细胞 肿瘤免疫 转录失调 代谢重编 亚群分型 

分 类 号：R730.3[医药卫生—肿瘤]