@article{Zhang2026, 
author = {Yangyang Zhang and Jingli Xu and Siwei Pan and Yuqi Wang and Qianyu Zhao and Ziyang Huang and Can Hu and Xiangdong Cheng},
title = {CD4+ T cells in cancer: dual roles, exhaustion, and therapeutic breakthroughs},
year = {2026},
journal = {Cancer Biology & Medicine},
volume = {23},
number = {1},
pages = {42-59},
keywords = {Mechanism of differentiation, dual role, T cell exhaustion, immunotherapeutic strategies, translational clinical applications},
url = {https://www.sciopen.com/article/10.20892/j.issn.2095-3941.2025.0414},
doi = {10.20892/j.issn.2095-3941.2025.0414},
abstract = {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.}
}