Translating γδ T Cell Biology From Bench to Bedside: Opportunities and Challenges in Viral and Cancer Immunotherapies

γδ T cells represent a vital subset of lymphocytes at the intersection of innate and adaptive immunity, distinguished by their unique T cell receptor (TCR) composition. Recent research has elucidated many aspects of γδ T cell biology using mouse systems, shedding light on their involvement in tissue residency, stress response, and roles in infection and tumor surveillance. However, important differences exist between human and murine γδ T cells, including divergence in TCR repertoire, tissue localization, and antigen recognition. Notably, human γδ T cells—particularly Vγ9Vδ2 and Vδ1 subsets—display distinct responses to infection, inflammation, aging, and malignancy, in ways not mirrored in rodent models. Current knowledge gaps and species‐specific variations complicate the direct translation of promising preclinical findings to clinical therapies targeting cancer, autoimmune, and infectious diseases, highlighting an urgent need for deeper investigation in human systems.This Research Topic aims to systematically address the remaining questions and barriers in γδ T cell research as it moves from basic discovery to clinical innovation. By focusing on the unique dynamics of human γδ T cell subsets—such as the age-associated expansion of Vδ1 cells and functional shifts following viral infections including HIV, HSV, and SARS-CoV-2—this collection will dissect the regulatory mechanisms underlying immune protection and therapeutic efficacy. Recent advances in single-cell multi-omics technologies, longitudinal human immunology studies, and the emergence of γδ T cell-based immunotherapeutics, such as CAR-T strategies, offer new avenues to interrogate the heterogeneity, exhaustion, and tissue adaptation of these cells. By incorporating comparative studies with non-human primates and rodents, contributors are encouraged to resolve key mechanistic questions and propose strategies to optimize γδ T cell–directed interventions for cancer, chronic, and infectious diseases.This Research Topic will focus on human γδ T cell biology and translational research while encouraging comparative analyses with non-human primates and rodent models to demarcate species-specific mechanisms and therapeutic targets. We invite submissions covering, but not limited to, the following themes:o Human γδ T cell repertoire and functional changes across the lifespan, with a focus on Vδ1 subset expansion in aging, infection, inflammation, auto-immune diseases, and cancero Effects of acute and chronic viral infections on γδ T cell phenotype, development, and functionalityo Comparative development, activation mechanisms, and immunoregulatory roles of γδ T cells in human, non-human primate, and rodent modelso Preclinical and clinical progress of γδ T cell–based immunotherapies, including cell and genetic engineering approaches (e.g., γδ CAR-T cells, viral therapy)o Agonists, antagonists, and novel strategies for the modulation of γδ T cell activity and subset balanceo The impact of tumor microenvironment and systemic inflammation on γδ T cell function and therapeutic outcomesPlease note that Dr. Mark Chiu is an employee of Tavotek, which is involved in drug discovery efforts using gamma-delta T cells. Topic editors: Tomozumi Imamichi, Mark Chiu Source: https://www.frontiersin.org/research-topics/78369/translating-t-cell-biology-from-bench-to-bedside-opportunities-and-challenges-in-viral-and-cancer-immunotherapies