Harnessing the power of Vδ2 cells in cancer immunotherapy

γδ T cells are a subset of T lymphocytes that have been implicated in immunosurveillance against infections and tumours. In the peripheral blood of humans the γδ T cell pool is made up predominantly of Vδ2 cells, which can detect both foreign and self-metabolites of the isoprenoid biosynthesis pathway. This unique axis of antigen recognition enables Vδ2 cells to respond to a range of pathogenic infections as well as perturbations in endogenous isoprenoid biosynthesis that can occur during cell stress and malignant transformation. There has been growing interest in Vδ2 cells as a potential avenue for cancer immunotherapy, and a number of strategies have been utilized in an attempt to boost the anti-tumour response of Vδ2 cells in patients. In this review we discuss critically the evidence that Vδ2 cells contribute to the cytotoxic response against tumours and evaluate current immunotherapeutic approaches that target these cells in cancer patients, with specific focus on their shortcomings and how they may be improved.