γδ T 细胞调节小细胞肺癌中的抗肿瘤免疫
γδ T cells modulate anti-tumor immunity in small cell lung cancer.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:γδT cells, a key subset of T cell for cancer immunotherapy.
γδT cells, a key subset of T cell for cancer immunotherapy.
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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。
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.
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