The emerging roles of γδ T cells in cancer immunotherapy

Current cancer immunotherapies are primarily predicated on alpha beta T cells, with a stringent dependence on MHC-mediated presentation of tumour-enriched peptides or unique neoantigens that can limit their efficacy and applicability in various contexts. After two decades of preclinical research and preliminary clinical studies involving very small numbers of patients, gamma delta T cells are now being explored as a viable and promising approach for cancer immunotherapy. The unique features of gamma delta T cells, including their tissue tropisms, antitumour activity that is independent of neoantigen burden and conventional MHC-dependent antigen presentation, and combination of typical properties of T cells and natural killer cells, make them very appealing effectors in multiple cancer settings. Herein, we review the main functions of gamma delta T cells in antitumour immunity, focusing on human gamma delta T cell subsets, with a particular emphasis on the differences between V delta 1(+) and V delta 2(+) gamma delta T cells, to discuss their prognostic value in patients with cancer and the key therapeutic strategies that are being developed in an attempt to improve the outcomes of these patients.

Automated summary

Current cancer immunotherapies are primarily based on alpha beta T cells, which have limitations in their efficacy and applicability. Gamma delta T cells, with unique features including tissue tropisms, independent antitumour activity, and properties of T cells and natural killer cells, are being explored as a promising approach for cancer immunotherapy. This review focuses on the functions and prognostic value of human gamma delta T cell subsets, particularly V delta 1(+) and V delta 2(+) cells, and discusses the therapeutic strategies being developed to improve outcomes for cancer patients.