基于肿瘤微环境中γδ T细胞可塑性的新见解

Yue-Zhong Wang, Yi Xu, Hui Chen, Jianmin Zhang, Wei He
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引用次数: 1

摘要

γδT细胞表达独特的T细胞受体(TCR)γ和TCRδ链,具有结构和功能的异质性。利用不同的γδTCR库或其他配体-受体相互作用,γδT细胞可以以不依赖于主要组织相容性复合体(MHC)的方式识别广泛的肿瘤相关抗原(TAAs),从而激活下游多效性效应。被招募到肿瘤微环境中的γδT细胞可以作为效应细胞介导癌症免疫监测。它们的优势在于能够以低突变量感知肿瘤,从而建立抵御病原体的第一道防线。活化的γδT细胞具有较强的细胞毒性和细胞因子分泌功能,是一种有效的抗肿瘤淋巴细胞,具有简单直接的识别模式和快速反应。然而,肿瘤浸润性γδT细胞的临床应用有一定的局限性。首先,暴露于复杂细胞因子网络的γδT细胞可能受到多种抑制机制的影响。此外,这些细胞表现出高度灵活和动态可塑性,极易分化为调节表型。这篇综述进一步强调了γδT细胞和其他免疫细胞之间的多样化串扰。身体的有效免疫往往表现为在相互制约下的平衡。因此,有必要深入了解在肿瘤微环境中发挥冲突作用的γδT细胞。这些细胞可能是最终介导肿瘤抑制和肿瘤促进之间拮抗反应偏差的关键因素。最后,回顾性分析了现有γδT细胞过继免疫疗法的激活策略和临床相关性。根据当前的挑战,需要探索创新的免疫疗法,最大限度地发挥γδT细胞的肿瘤杀伤功效,并减弱或消除肿瘤免疫抑制。希望能准确预测宿主免疫状态,逐步推进γδT细胞精准个体化用药。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel insights based on the plasticity of γδ T cells in the tumor microenvironment
γδ T cells express unique T cell receptor (TCR) γ and TCR δ chains, with structural and functional heterogeneity. Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)-independent manner, thereby activating downstream pleiotropic effects. γδ T cells recruited into the tumor microenvironment can act as effector cells to mediate cancer immune surveillance. Their advantage lies in the ability to perceive tumors with a low mutation load, thus establishing the first line of defense against pathogens. Activated γδ T cells exhibit strong cytotoxic activity and cytokine secretion functions and are effective antitumor lymphocytes with simple and direct recognition modes and rapid responses. However, the clinical application of tumor-infiltrating γδ T cells has certain limitations. First, γδ T cells exposed to complicated cytokine networks are potentially affected by multiple inhibitory mechanisms. Additionally, these cells show highly flexible and dynamic plasticity and are extremely easily polarized into regulatory phenotypes. This review further emphasizes the diversified cross-talk between γδ T cells and other immune cells. Effective immunity of the body is often manifested by counterbalance under mutual restriction. Therefore, an in-depth understanding of γδ T cells that play conflicting roles in the tumor microenvironment is necessary. These cells may be a key factor ultimately mediating the deviation of the antagonistic response between tumor inhibition and tumor promotion. Finally, it retrospectively analyze the activation strategies and clinical relevance of existing γδ T cell adoptive immunotherapies. According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. It is hoped that the host immune status can be accurately predicted and gradually advance γδ T cell precise individualized medicine.
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