The promise of γδT cells and the γδT cell receptor for cancer immunotherapy

Abstract

γδT cells form an important part of adaptive immune responses against infections and malignant transformation. The molecular targets of human γδT cell receptors (TCRs) remain largely unknown, but recent studies have confirmed the recognition of phosphorylated prenyl metabolites, lipids in complex with CD1 molecules and markers of cellular stress. All of these molecules are upregulated on various cancer types, highlighting the potential importance of the γδT cell compartment in cancer immunosurveillance and paving the way for the use of γδTCRs in cancer therapy. Ligand recognition by the γδTCR often requires accessory/co-stimulatory stress molecules on both T cells and target cells this cellular stress context therefore provides a failsafe against harmful self-reactivity. Unlike αβ T cells, γδT cells recognise their targets irrespective of HLA haplotype and therefore offer exciting possibilities for off-the-shelf, pan-population cancer immunotherapies. Here, we present a review of known ligands of human γδT cells and discuss the promise of harnessing these cells for cancer treatment.