Hierarchical transcriptional network governing heterogeneous T cell exhaustion and its implications for immune checkpoint blockade

Frontiers in Immunology

Immunology

Wuhao Li¹  Hui Wang¹  Yangjing Zhao¹  Qixiang Shao²  Weihong Tian³  Xuanwen Bao⁴  Weili Cai⁵  Miaomiao Jia⁶  Wangzhi Wei⁷  Gaofeng Qin⁷  Yu Zhang⁷ 

[1] Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China;Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China;Institute of Medical Genetics and Reproductive Immunity, School of Medical Science and Laboratory Medicine, Jiangsu College of Nursing, Huai’an, Jiangsu, China;Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China;Life Science Institute, Jinzhou Medical University, Jinzhou, Liaoning, China;Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University & Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Hangzhou, Zhejiang, China;Institute of Medical Genetics and Reproductive Immunity, School of Medical Science and Laboratory Medicine, Jiangsu College of Nursing, Huai’an, Jiangsu, China;Jiaxing Key Laboratory of Pathogenic Microbiology, Jiaxing Center for Disease Control and Prevention, Jiaxing, Zhejiang, China;Life Science Institute, Jinzhou Medical University, Jinzhou, Liaoning, China;

关键词: T cell exhaustion;    heterogeneous;    T cell factor 1;    chronic TCR stimulation;    TOX;    PD-1;    immune checkpoint blockade;   

DOI  :  10.3389/fimmu.2023.1198551

 received in 2023-04-01, accepted in 2023-06-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

The fundamental principle of immune checkpoint blockade (ICB) is to protect tumor-infiltrating T cells from being exhausted. Despite the remarkable success achieved by ICB treatment, only a small group of patients benefit from it. Characterized by a hypofunctional state with the expression of multiple inhibitory receptors, exhausted T (Tex) cells are a major obstacle in improving ICB. T cell exhaustion is a progressive process which adapts to persistent antigen stimulation in chronic infections and cancers. In this review, we elucidate the heterogeneity of Tex cells and offer new insights into the hierarchical transcriptional regulation of T cell exhaustion. Factors and signaling pathways that induce and promote exhaustion are also summarized. Moreover, we review the epigenetic and metabolic alterations of Tex cells and discuss how PD-1 signaling affects the balance between T cell activation and exhaustion, aiming to provide more therapeutic targets for applications of combinational immunotherapies.

【 授权许可】

Unknown   
Copyright © 2023 Tian, Qin, Jia, Li, Cai, Wang, Zhao, Bao, Wei, Zhang and Shao