gamma delta T cells represent a unique and versatile subset of T cells characterized by the expression of T-cell receptors (TCRs) composed of gamma and delta chains. Unlike conventional alpha beta T cells, gamma delta T cells do not require major histocompatibility complex (MHC)-dependent antigen presentation for activation, enabling them to recognize and respond to a wide array of antigens, including phosphoantigens, stress-induced ligands, and tumor-associated antigens. While gamma delta T cells are relatively rare in peripheral blood, they are enriched in peripheral tissues such as the skin, intestine, and lung. These cells play a crucial role in tumor immunotherapy by exerting direct cytotoxicity through the production of inflammatory cytokines (e.g., interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-17 (IL-17)) and cytotoxic molecules (e.g., perforin and granzyme). Recent advances in gamma delta T cell research have elucidated their mechanisms of tumor recognition, including the detection of phosphoantigens and stress-induced ligands like MICA (MHC class I polypeptide-related sequence A), MICB (MHC class I polypeptide-related sequence B), and ULBP (UL16-binding protein). Furthermore, various strategies to enhance gamma delta T cell-based tumor immunotherapy have been developed, such as in vitro expansion using phosphoantigen-based therapies, cytokine stimulation, and chimeric antigen receptor (CAR)-gamma delta T cell engineering. These advancements have shown promising results in both preclinical and clinical settings, paving the way for gamma delta T cells to become a powerful tool in cancer immunotherapy. This review highlights the key mechanisms, functions, and strategies to harness the potential of gamma delta T cells for effective tumor immunotherapy.
基金:
National Natural Science Foundation of China [81802504]; Sichuan Science and Technology Program [2025YFHZ0123]; Chengdu Science and Technology Program [2024-YF05-01315-SN, 2024HX008]; Guangxi Natural Science Foundation [2020GXNSFAA159070, 2022GXNSFAA035608]
第一作者机构:[1]Guangxi Univ Chinese Med, Inst Tradit Chinese & Zhuang Yao Ethn Med, Guangxi Key Lab Efficacy Study Chinese Mat Med, Nanning, Guangxi, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[6]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Crit Care Med, Chengdu, Sichuan, Peoples R China[7]Sichuan Acad Med Sci, Ctr Organ Transplantat, Clin Immunol Translat Med Key Lab Sichuan Prov, Chengdu, Sichuan, Peoples R China[8]Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China
推荐引用方式(GB/T 7714):
Lv Jianzhen,Liu Zheng,Ren Xiangting,et al.γδT cells, a key subset of T cell for cancer immunotherapy[J].FRONTIERS IN IMMUNOLOGY.2025,16:doi:10.3389/fimmu.2025.1562188.
APA:
Lv, Jianzhen,Liu, Zheng,Ren, Xiangting,Song, Siyuan,Zhang, Yan&Wang, Yi.(2025).γδT cells, a key subset of T cell for cancer immunotherapy.FRONTIERS IN IMMUNOLOGY,16,
MLA:
Lv, Jianzhen,et al."γδT cells, a key subset of T cell for cancer immunotherapy".FRONTIERS IN IMMUNOLOGY 16.(2025)