Cancer continues to be a leading cause of global mortality, accounting for approximately 10 million fatalities annually (Zaimy et al., 2017). Tumor cells evade immune surveillance through multiple mechanisms, including creating immunosuppressive microenvironments and enhancing inhibitory pathways (Zhang and Zhang, 2020), which present significant challenges to conventional therapies, including reduced efficacy and high recurrence rates. Tumor immunotherapy aims to reactivate and maintain the tumor-immune cycle by examining the relationship between the tumor-stromal microenvironment, inflammation, and immune system, thereby controlling and eliminating tumors (Li et al., 2022a). Clinical studies have indicated that immunotherapy responders live longer with fewer instances of metastasis, suggesting its potential to combat cancer spread (Cha et al., 2020). Among the various immunotherapies, γδ T cell therapy has attracted attention because of its remarkable effect and great potential in antitumor therapy, earning the title of "ace army" in tumor therapy and gaining prominence in contemporary immunotherapy research.

The T-cell receptor (TCR) was discovered in the late 20th century and is primarily classified into αβ and γδ types, with the majority of T cells expressing the αβ TCR (Kirsch et al., 2015). Brenner et al. first identified γδ T cells using antibodies developed with peptides that encode the sequence of the T-cell antigen receptor γ gene (Brenner et al., 1986). The discovered γδ T cells consisted of γ and δ chains (Wiesheu and Coffelt, 2024). Although γδ T cells are among the earliest T cell populations to emerge during mammalian ontogeny, they constitute a minor fraction (1–5 %) of peripheral blood lymphocytes (Vantourout and Hayday, 2013). Compared to B lymphocytes and αβ T lymphocytes, γδ T cells are a numerically minor population in the immune system and have historically been overlooked. However, their distinctiveness lies in their ability to exhibit both adaptive and rapid innate-like responses (Muro et al., 2019). This allows γδ T cells to respond promptly at the onset of the immune response. At the same time, γδ T cells have a wider range of antigen recognition abilities; they can identify antigens presented by traditional MHC molecules as well as non-MHC-restricted antigens, such as heat shock proteins and phospholipid molecules (Adams et al., 2015). This unique antigen recognition mechanism enables γδ T cells to recognize and attack tumor cells more effectively in the tumor microenvironment. In summary, γδ T cells are versatile and comprehensive, possessing both non-specific and specific immune characteristics, as well as the dual functions of killing and regulation, playing a crucial role in the body's immune response that other immune cells cannot replace (Bonneville et al., 2010, Hayday et al., 2024). With extensive research on the biological properties and antitumor mechanisms of γδ T cells, their application in cancer therapy is becoming increasingly promising. To enhance our understanding of γδ T cells, this review provides an overview of the classification of γδ T cells, mechanisms underlying tumor-killing recognition and their influencing factors, therapeutic pathways, ex vivo, and clinical trials. These studies highlight the potential and significance of γδ T cells in cancer therapy.