Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Heidelberg, VIC, Australia.
Department of Medicine, University of Melbourne, Parkville, VIC, Australia.
Front Immunol. 2022 Jul 11;13:894315. doi: 10.3389/fimmu.2022.894315. eCollection 2022.
A growing number of studies have shown that γδ T cells play a pivotal role in mediating the clearance of tumors and pathogen-infected cells with their potent cytotoxic, cytolytic, and unique immune-modulating functions. Unlike the more abundant αβ T cells, γδ T cells can recognize a broad range of tumors and infected cells without the requirement of antigen presentation major histocompatibility complex (MHC) molecules. Our group has recently demonstrated parts of the mechanisms of T-cell receptor (TCR)-dependent activation of Vγ9Vδ2 T cells by tumors following the presentation of phosphoantigens, intermediates of the mevalonate pathway. This process is mediated through the B7 immunoglobulin family-like butyrophilin 2A1 (BTN2A1) and BTN3A1 complexes. Such recognition results in activation, a robust immunosurveillance process, and elicits rapid γδ T-cell immune responses. These include targeted cell killing, and the ability to produce copious quantities of cytokines and chemokines to exert immune-modulating properties and to interact with other immune cells. This immune cell network includes αβ T cells, B cells, dendritic cells, macrophages, monocytes, natural killer cells, and neutrophils, hence heavily influencing the outcome of immune responses. This key role in orchestrating immune cells and their natural tropism for tumor microenvironment makes γδ T cells an attractive target for cancer immunotherapy. Here, we review the current understanding of these important interactions and highlight the implications of the crosstalk between γδ T cells and other immune cells in the context of anti-tumor immunity.
越来越多的研究表明，γδ T 细胞在介导肿瘤和病原体感染细胞的清除中发挥着关键作用，具有强大的细胞毒性、细胞溶解作用和独特的免疫调节功能。与更为丰富的 αβ T 细胞不同，γδ T 细胞可以识别广泛的肿瘤和感染细胞，而不需要抗原呈递主要组织相容性复合体（MHC）分子。我们的研究小组最近证明了部分机制，即在磷酸抗原呈递后，T 细胞受体（TCR）依赖性激活 Vγ9Vδ2 T 细胞，这些抗原是甲羟戊酸途径的中间产物。这个过程是通过 B7 免疫球蛋白家族样但丁醇蛋白 2A1（BTN2A1）和 BTN3A1 复合物介导的。这种识别导致激活、强大的免疫监视过程，并引发快速的 γδ T 细胞免疫反应。这些反应包括靶向细胞杀伤，以及产生大量细胞因子和趋化因子的能力，以发挥免疫调节特性并与其他免疫细胞相互作用。这个免疫细胞网络包括 αβ T 细胞、B 细胞、树突状细胞、巨噬细胞、单核细胞、自然杀伤细胞和中性粒细胞，因此对免疫反应的结果有重大影响。γδ T 细胞在协调免疫细胞及其对肿瘤微环境的天然趋向性方面发挥着关键作用，使其成为癌症免疫治疗的一个有吸引力的靶点。在这里，我们综述了这些重要相互作用的最新理解，并强调了 γδ T 细胞与其他免疫细胞之间的串扰在抗肿瘤免疫中的意义。
