γδ T cells in colorectal and liver cancer

Among tissue-resident immune cells, γδ T cells have a unique role in local immune surveillance. Under homeostatic conditions, they control tissue integrity and maintain the epithelial barrier. In contrast to conventional αβ T cells, γδ T cells sense stress-induced cellular alterations and, therefore, can recognize transformed cells independently of MHC (HLA in humans) molecules. In colorectal cancer and hepatocellular carcinoma, γδ T cells constitute an important part of the antitumour immune response. However, there is evidence that γδ T cells can also promote tumorigenesis. In this Review, we present basic features of γδ T cells and their distribution and function in the context of the local immune response. We discuss the ligands and antigens recognized by circulating and tissue-resident human γδ T cells, as well as the functional diversity of γδ T cell subsets within tumour-infiltrating T cells in colorectal and liver cancer. Given their potent cytotoxic activity and HLA-independent mode of action, there is increasing interest in harnessing γδ T cells for application in cancer immunotherapy. We therefore discuss the current status and future challenges of using γδ T cells as an innovative immunotherapeutic strategy for gastrointestinal and liver cancer.