Gamma delta T cells and their immunotherapeutic potential in cancer

Gamma-delta (γδ) T cells are a unique subset of T lymphocytes that play diverse roles in immune responses, bridging innate and adaptive immunity. With growing interest in their potential for cancer immunotherapy, a comprehensive and inclusive exploration of γδ T cell families, their development, activation mechanisms, functions, therapeutic implications, and current treatments is essential. This review aims to provide an inclusive and thorough discussion of these topics. Through our discussion, we seek to uncover insights that may harbinger innovative immunotherapeutic strategies. Beginning with an overview of γδ T cell families including Vδ1, Vδ2, and Vδ3, this review highlights their distinct functional properties and contributions to anti-tumor immunity. Despite γδ T cells exhibiting both anti-tumor and pro-tumor activities, our review elucidates strategies to harness the anti-tumor potential of γδ T cells for therapeutic benefit. Moreover, our paper discusses the structural intricacies of the γδ T cell receptor and its significance in tumor recognition. Additionally, this review examines conventional and emerging γδ T cell therapies, encompassing both non-engineered and engineered approaches, with a focus on their efficacy and safety profiles in clinical trials. From multifunctional capabilities to diverse tissue distribution, γδ T cells play a pivotal role in immune regulation and surveillance. By analyzing current research findings, this paper offers insights into the dynamic landscape of γδ T cell-based immunotherapies, underscoring their promise as a potent armamentarium against cancer. Furthermore, by dissecting the complex biology of γδ T cells, we learn valuable information about the anti-cancer contributions of γδ T cells, as well as potential targets for immunotherapeutic interventions.