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γδT 细胞,癌症免疫治疗中 T 细胞的关键亚群

英文原题:γδT cells, a key subset of T cell for cancer immunotherapy.

查看英文原题

γδT cells, a key subset of T cell for cancer immunotherapy.

PubMed 2025/03/28(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

γδT 细胞代表了一类独特且多功能的 T 细胞亚群,其特征是表达由 γ 链和 δ 链组成的 T 细胞受体 (TCR)。与传统的 αβT 细胞不同,γδT 细胞的激活不依赖于主要组织相容性复合体 (MHC) 依赖的抗原提呈,这使得它们能够识别并响应多种抗原,包括磷酸抗原、应激诱导配体和肿瘤相关抗原。虽然 γδT 细胞在外周血中相对罕见,但它们在皮肤、肠道和肺等外周组织中富集。这些细胞通过产生炎症细胞因子(例如,干扰素-γ (IFN-γ)、肿瘤坏死因子-α (TNF-α) 和白细胞介素-17 (IL-17))和细胞毒性分子(例如,穿孔素和颗粒酶)发挥直接细胞毒性作用,在肿瘤免疫治疗中起着至关重要的作用。γδT 细胞研究的最新进展阐明了其肿瘤识别机制,包括检测磷酸抗原和应激诱导配体,如 MICA (MHC I 类多肽相关序列 A)、MICB (MHC I 类多肽相关序列 B) 和 ULBP (UL16 结合蛋白)。

此外,已开发出多种增强基于 γδT 细胞的肿瘤免疫治疗的策略,例如使用基于磷酸抗原的疗法进行体外扩增、细胞因子刺激以及嵌合抗原受体 (CAR)-γδT 细胞工程。这些进展在临床前和临床环境中均显示出有希望的结果,为 γδT 细胞成为癌症免疫治疗中的强大工具铺平了道路。本综述重点介绍了利用 γδT 细胞进行有效肿瘤免疫治疗的关键机制、功能和策略。

展开英文摘要原文

γδT cells represent a unique and versatile subset of T cells characterized by the expression of T-cell receptors (TCRs) composed of γ and δ chains. Unlike conventional αβT cells, γδT 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 γδT 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-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-17 (IL-17)) and cytotoxic molecules (e. g. , perforin and granzyme).

Recent advances in γδT 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 γδT cell-based tumor immunotherapy have been developed, such as in vitro expansion using phosphoantigen-based therapies, cytokine stimulation, and chimeric antigen receptor (CAR)-γδT cell engineering. These advancements have shown promising results in both preclinical and clinical settings, paving the way for γδT cells to become a powerful tool in cancer immunotherapy. This review highlights the key mechanisms, functions, and strategies to harness the potential of γδT cells for effective tumor immunotherapy.

论文信息

作者
Lv J、Liu Z、Ren X、Song S、Zhang Y、Wang Y
第一作者单位
Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Institute of Traditional Chinese and Zhuang-Yao Ethnic Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, China.China
通讯作者单位
Department of Critical Care Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.China
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 40226616 · DOI 10.3389/fimmu.2025.1562188