Anticancer mechanisms and applications based on γδ T cells in cancer immunotherapy

Cancer continues to be a major global health challenge, posing a substantial threat to human well-being, with a high mortality rate. Although recent advancements have significantly enhanced the effectiveness of cancer treatment, the percentage of metastasis and recurrence remains high. Immunotherapy has emerged as a potent cancer treatment method with high specificity and limited or manageable side effects; thus, it has garnered considerable attention. Among the promising candidates for the next generation of tumor immunotherapy are γδ T cells, which are effector lymphocytes and a subpopulation of T cells characterized by receptors composed of γ and δ chains, and are a unique cell type that mediates between intrinsic and specific immunity. Additionally, γδ T cells are capable of secreting a variety of cytokines, playing a crucial role in both multiple homeostatic and disease-associated processes in vivo, and perform a significant function in immune surveillance and defense. Unlike αβ T cells, γδ T cells possess an antigen-specific recognition capability that is neither restricted by the major histocompatibility complex (MHC) nor dependent on antigen-presenting cells. Both foundational research and clinical studies have demonstrated that γδ T cells derived from peripheral blood or tumor tissues and expanded using nitrogen-containing phosphates and interleukin (IL)-2 exhibit cytotoxic effects against various tumor types. Therefore, to achieve a thorough and comprehensive understanding of the practical applications and functional mechanisms of γδ T cells in oncology, we present a review of advancements in research on γδ T cell immunology and its application and mechanism in cancer treatment.