Targeting T regulatory(T_(reg))cells in immunotherapy-resistant cancers  

作　　者：Pavlina Spiliopoulou Paramjit Kaur Tracey Hammett Giusy Di Conza Michael Lahn 

机构地区：[1]Department of Drug Development Program,Phase I Unit,Beatson West of Scotland Cancer Center,Glasgow G120YN,UK [2]School of Cancer Sciences,University of Glasgow,Glasgow G611BD,UK [3]Department of Oncology Clinical Development,iOnctura SA,Geneva 1202,Switzerland

出　　处：《Cancer Drug Resistance》2024年第1期1053-1077,共25页癌症耐药(英文)

摘　　要：Primary or secondary(i.e.,acquired)resistance is a common occurrence in cancer patients and is often associated with high numbers of T regulatory(T_(reg))cells(CD4^(+)CD25^(+)FOXP3^(+)).The approval of ipilimumab and the development of similar pharmacological agents targeting cell surface proteins on T_(reg)cells demonstrates that such intervention may overcome resistance in cancer patients.Hence,the clinical development and subsequent approval of Cytotoxic T Lymphocyte Antigen-4(CTLA-4)targeting agents can serve as a prototype for similar agents.Such new agents aspire to be highly specific and have a reduced toxicity profile while increasing effector T cell function or effector T/T regulatory(T_(eff)/T_(reg))ratio.While clinical development with large molecules has shown the greatest advancement,small molecule inhibitors that target immunomodulation are increasingly entering early clinical investigation.These new small molecule inhibitors often target specific intracellular signaling pathways[e.g.,phosphoinositide-3-kinase delta(PI3K-δ)]that play an important role in regulating the function of T_(reg)cells.This review will summarize the lessons currently applied to develop novel clinical agents that target T_(reg)cells.

关 键 词：Primary and secondary resistance T regulatory cells flow cytometry mass cytometry hyperprogression 

分 类 号：R73[医药卫生—肿瘤]