Targeting the epigenome to reinvigorate T cells for cancer immunotherapy  

作　　者：Dian Xiong Lu Zhang Zhi-Jun Sun 

机构地区：[1]State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Frontier Science Center for Immunology and Metabolism,Wuhan University,Wuhan 430079,China [2]Department of Oral Maxillofacial-Head Neck Oncology,School and and Hospital of Stomatology,Wuhan University,Wuhan 430079,China

出　　处：《Military Medical Research》2024年第6期863-886,共24页军事医学研究(英文版)

基　　金：supported by the National Natural Science Foundation of China(82273202,82370948,82072996,82170941);the Fundamental Research Funds for the Central Universities(2042022dx0003);the Hubei Province International Science and Technology Cooperation Project(2021EHB027);the National Key Research and Development Program(2022YFC2504200).

摘　　要：Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),which is termed T cell exhaustion.This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment(TIME).Simultaneously,tumorigenesis entails robust reshaping of the epigenetic landscape,potentially instigating T cell exhaustion.In this review,we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion,and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies.Finally,we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.

关 键 词：Epigenetic therapy Immune checkpoint blockade Combination therapy T cell exhaustion Immune macroenvironment Spatial immune contexture Immunometabolism Cancer microbiome 

分 类 号：R73[医药卫生—肿瘤]