CD4^(+)T cells in cancer:dual roles,exhaustion,and therapeutic breakthroughsOA
In recent years the crucial role of CD4^(+)T cells in tumor immunomodulation has garnered increasing recognition.While conventional cancer immunotherapy research has predominantly focused on the cytotoxic function of CD8+T cells,emerging evidence has now shown that CD4^(+)T cells enhance antitumor immunity by delivering co-stimulatory signals,secreting cytokines,and promoting cytotoxic T lymphocyte(CTL)activation and display unique immunoregulatory capabilities through direct tumor cell killing or remodeling of the tumor microenvironment.The high heterogeneity and functional plasticity of CD4^(+)T cell subsets significantly influence clinical responses to immunotherapy with underlying mechanisms involving multi-level regulatory networks,including epigenetic modulation and metabolic reprogramming.Deciphering the functional heterogeneity of CD4^(+)T cells and the interactions with the tumor microenvironment will provide essential mechanistic insights for next-generation immunotherapies,such as immune checkpoint inhibitors and chimeric antigen receptor T(CAR-T)therapies,thereby advancing personalized treatment paradigms.
Yangyang Zhang;Jingli Xu;Siwei Pan;Yuqi Wang;Qianyu Zhao;Ziyang Huang;Can Hu;Xiangdong Cheng
College of Pharmaceutical Sciences,Zhejiang University of Technology,Hangzhou 310014,China Department of Gastric Surgery,Zhejiang Cancer Hospital,Hangzhou 310014,China Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310014,China Zhejiang Key Laboratory of Prevention,Diagnosis and Therapy for Gastrointestinal Cancer,Hangzhou 310014,China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer,Zhejiang Cancer Hospital,Hangzhou 310014,ChinaDepartment of Gastric Surgery,Zhejiang Cancer Hospital,Hangzhou 310014,China Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310014,China Zhejiang Key Laboratory of Prevention,Diagnosis and Therapy for Gastrointestinal Cancer,Hangzhou 310014,China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer,Zhejiang Cancer Hospital,Hangzhou 310014,ChinaDepartment of Gastric Surgery,Zhejiang Cancer Hospital,Hangzhou 310014,China Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310014,China Zhejiang Key Laboratory of Prevention,Diagnosis and Therapy for Gastrointestinal Cancer,Hangzhou 310014,China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer,Zhejiang Cancer Hospital,Hangzhou 310014,ChinaDepartment of Gastric Surgery,Zhejiang Cancer Hospital,Hangzhou 310014,China Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310014,China Zhejiang Key Laboratory of Prevention,Diagnosis and Therapy for Gastrointestinal Cancer,Hangzhou 310014,China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer,Zhejiang Cancer Hospital,Hangzhou 310014,ChinaDepartment of Gastric Surgery,Zhejiang Cancer Hospital,Hangzhou 310014,China Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310014,China Zhejiang Key Laboratory of Prevention,Diagnosis and Therapy for Gastrointestinal Cancer,Hangzhou 310014,China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer,Zhejiang Cancer Hospital,Hangzhou 310014,ChinaCollege of Pharmaceutical Sciences,Zhejiang University of Technology,Hangzhou 310014,China Department of Gastric Surgery,Zhejiang Cancer Hospital,Hangzhou 310014,China Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310014,China Zhejiang Key Laboratory of Prevention,Diagnosis and Therapy for Gastrointestinal Cancer,Hangzhou 310014,China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer,Zhejiang Cancer Hospital,Hangzhou 310014,ChinaDepartment of Gastric Surgery,Zhejiang Cancer Hospital,Hangzhou 310014,China Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310014,China Zhejiang Key Laboratory of Prevention,Diagnosis and Therapy for Gastrointestinal Cancer,Hangzhou 310014,China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer,Zhejiang Cancer Hospital,Hangzhou 310014,ChinaDepartment of Gastric Surgery,Zhejiang Cancer Hospital,Hangzhou 310014,China Hangzhou Institute of Medicine(HIM),Chinese Academy of Sciences,Hangzhou 310014,China Zhejiang Key Laboratory of Prevention,Diagnosis and Therapy for Gastrointestinal Cancer,Hangzhou 310014,China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer,Zhejiang Cancer Hospital,Hangzhou 310014,China
医药卫生
Mechanism of differentiationdual roleT cell exhaustionimmunotherapeutic strategiestranslational clinical applications
《Cancer Biology & Medicine》 2026 (1)
P.42-59,18
supported by The National Key Research and Development Program of China(Grant No.2021YFA0910100)Healthy Zhejiang One Million People Cohort(Grant No.K-20230085)supported by National Natural Science Foundation of China(Grant Nos.82304946 and 82573745)Post-doctoral Innovative Talent Support Program(Grant No.BX2023375)567 Foundation of Zhejiang Province(Grant No.LMS25H160006)supported by the National Natural Science Foundation of China(Grant No.82473489)the Medical Science and Technology Project of Zhejiang Province(Grant No.WKJ-ZJ-2202)the Natural Science Foundation of Zhejiang Province(Grant No.LBD24H290001)supported by the National Natural Science Foundation of China(Grant No.82403546).
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