[关键词]
[摘要]
γδT细胞是一类表达γδTCR异源二聚体的特殊固有免疫T细胞。过去,缺乏对其全面系统的基础研究,在其发育、分化、增殖、活化、效应和耗竭等所有环节仍有很多问题尚不清楚。然而,因为成熟的γδT细胞优势定植于皮肤、消化道、呼吸道、生殖道等肿瘤高发的黏膜组织,能以MHC非限制性的方式直接识别和杀伤多种肿瘤细胞,在肿瘤免疫治疗领域具有不可替代的优势,近年来其应用异军突起,发展迅速,也因此反过来促进了基础研究的深入,取得了一些亮眼的进展。本文对2023 年γδT 细胞在肿瘤免疫治疗领域的重大进展进行述评,主要集中在γδT 细胞肿瘤抗原识别机制、肿瘤微环境中γδT 细胞的功能调控、γδT 细胞抗肿瘤细胞毒活性的机制、新型基于γδT 细胞的肿瘤免疫治疗协同增效策略四个方面,以期推动γδT 细胞在肿瘤免疫治疗领域的进一步发展,为临床γδT 细胞应用协同增效的策略提供新的思路。
[Key word]
[Abstract]
γδT cell is a unique kind of innate immune T cell expressing T cell receptor γ and δ chain heterodimer. There is a lack of comprehensive and systematic basic research in the development, differentiation, proliferation, activation, effect and exhaustion of γδT cell that many main questions are remaining unclear. However, mature γδT cells predominantly colonize mucosal tissues with a high incidence of tumors, such as skin, digestive tract, respiratory tract, and reproductive tract, and can directly recognize and kill a variety of tumor cells without major histocompatibility complex (MHC) restriction, which has irreplaceable advantages in the field of tumor immunotherapy. In recent years, the application of γδT cells have surged and developed rapidly, which, in turn, contributed to the deepening of basic research, and thus some brilliant progress has been made. In this paper, we enumerate the major progress of γδT cells in tumor immunotherapy in 2023, mainly focusing on the mechanism of tumor antigen recognition by γδT cells, the functional regulation of γδT cells in the tumor microenvironment, the mechanism of anti-tumor cytotoxicity of γδT cells, and the new synergistic strategy of tumor immunotherapy based on γδT cells. It is expected to promote the further development of γδT cells in the field of tumour immunotherapy and provide new insights into the synergistic strategy of γδT cells in clinical application.
[中图分类号]
[基金项目]
中国医学科学院创新工程项目(No.2021-I2M-1-035);国家自然科学基金项目(No.32270915, No.U20A20374,No.31970843,No.82071791, No.81972886);北京市科委中关村管委会创新药方向课题(No.Z221100007922040);国家重点研发计划项目(No.2022YFC3602004);常州市科技支撑计划项目(No.CE20215008)