γδ T cells: origin and fate, subsets, diseases and immunotherapy

• Published in: Signal transduction and targeted therapy 2023-11, Vol.8 (1), p.434-434, Article 434
• Main Authors: Hu, Yi, Hu, Qinglin, Li, Yongsheng, Lu, Ligong, Xiang, Zheng, Yin, Zhinan, Kabelitz, Dieter, Wu, Yangzhe
• Format: Article
• Language: English
• Subjects: 631/250/1619; 631/250/2152; 631/250/262; 631/250/580; 692/699/249; Cancer Research; Cell Biology; Cytokines; Humans; Immune system; Immunotherapy; Infectious diseases; Internal Medicine; Lymphocytes; Lymphocytes T; Malignancy; Medicine; Medicine & Public Health; Microenvironments; Neoplasms - genetics; Neoplasms - therapy; Oncology; Pathology; Receptors, Antigen, T-Cell, gamma-delta - genetics; Review Article; Solid tumors; T cell receptors; T-Lymphocyte Subsets; Tumor Microenvironment; Tumors
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-023-01653-8

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential of immune renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering the use of allogeneic Vδ2 + γδ T cells for treating late-stage solid tumors and tuberculosis patients. However, we recognize untapped potential and optimization opportunities to fully harness γδ T cell effector functions in immunotherapy. This review aims to thoroughly examine γδ T cell immunology and its role in diseases. Initially, we elucidate functional differences between γδ T cells and their αβ T cell counterparts. We also provide an overview of major milestones in γδ T cell research since their discovery in 1984. Furthermore, we delve into the intricate biological processes governing their origin, development, fate decisions, and T cell receptor (TCR) rearrangement within the thymus. By examining the mechanisms underlying the anti-tumor functions of distinct γδ T cell subtypes based on γδTCR structure or cytokine release, we emphasize the importance of accurate subtyping in understanding γδ T cell function. We also explore the microenvironment-dependent functions of γδ T cell subsets, particularly in infectious diseases, autoimmune conditions, hematological malignancies, and solid tumors. Finally, we propose future strategies for utilizing allogeneic γδ T cells in tumor immunotherapy. Through this comprehensive review, we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers of γδ T cells, ultimately contributing to further advancements in harnessing the therapeutic potential of γδ T cells.