The emerging roles of γδ T cells in cancer immunotherapy

Current cancer immunotherapies are primarily predicated on αβ 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, γδ T cells are now being explored as a viable and promising approach for cancer immunotherapy. The unique features of γδ 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 γδ T cells in antitumour immunity, focusing on human γδ T cell subsets, with a particular emphasis on the differences between Vδ1⁺ and Vδ2⁺ γδ 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.