Oncology Department, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Front Immunol. 2024 Aug 26;15:1466266. doi: 10.3389/fimmu.2024.1466266. eCollection 2024.
Gamma/delta T (γδ T)cells possess a unique mechanism for killing tumors, making them highly promising and distinguished among various cell therapies for tumor treatment. This review focuses on the major histocompatibility complex (MHC)-independent recognition of antigens and the interaction between γδ T cells and solid tumor cells. A comprehensive review is provided regarding the classification of human gamma-delta T cell subtypes, the characteristics and mechanisms underlying their functions, as well as their r545egulatory effects on tumor cells. The involvement of γδ T cells in tumorigenesis and migration was also investigated, encompassing potential therapeutic targets such as apoptosis-related molecules, the TNF receptor superfamily member 6(FAS)/FAS Ligand (FASL) pathways, butyrophilin 3A-butyrophilin 2A1 (BTN3A-BTN2A1) complexes, and interactions with CD4, CD8, and natural killer (NK) cells. Additionally, immune checkpoint inhibitors such as programmed cell death protein 1/Programmed cell death 1 ligand 1 (PD-1/PD-L1) have the potential to augment the cytotoxicity of γδ T cells. Moreover, a review on gamma-delta T cell therapy products and their corresponding clinical trials reveals that chimeric antigen receptor (CAR) gamma-delta T therapy holds promise as an approach with encouraging preclinical outcomes. However, practical issues pertaining to manufacturing and clinical aspects need resolution, and further research is required to investigate the long-term clinical side effects of CAR T cells. In conclusion, more comprehensive studies are necessary to establish standardized treatment protocols aimed at enhancing the quality of life and survival rates among tumor patients utilizing γδ T cell immunotherapy.
γ/δ T(γδ T)细胞具有独特的杀伤肿瘤机制,使其在各种肿瘤治疗的细胞疗法中极具应用前景和特色。本综述重点关注主要组织相容性复合物(MHC)非依赖性抗原识别以及γδ T 细胞与实体瘤细胞之间的相互作用。全面回顾了人类γδ T 细胞亚群的分类、其功能的特征和机制,以及它们对肿瘤细胞的调节作用。还研究了 γδ T 细胞在肿瘤发生和迁移中的作用,包括与细胞凋亡相关的分子、肿瘤坏死因子受体超家族成员 6(FAS)/FAS 配体(FASL)途径、黏蛋白 3A-黏蛋白 2A1(BTN3A-BTN2A1)复合物以及与 CD4、CD8 和自然杀伤(NK)细胞的相互作用等潜在治疗靶点。此外,免疫检查点抑制剂,如程序性细胞死亡蛋白 1/程序性死亡受体 1 配体 1(PD-1/PD-L1),有可能增强 γδ T 细胞的细胞毒性。此外,综述了 γδ T 细胞治疗产品及其相应的临床试验,表明嵌合抗原受体(CAR)γδ T 治疗具有令人鼓舞的临床前结果,具有应用前景。然而,在制造和临床方面仍存在实际问题需要解决,并且需要进一步研究来调查 CAR T 细胞的长期临床副作用。总之,需要进行更全面的研究,以建立基于 γδ T 细胞免疫治疗的标准化治疗方案,旨在提高肿瘤患者的生活质量和生存率。