The role of the common gamma-chain family cytokines in gamma delta T cell-based anti-cancer immunotherapy

Cytokines of the common gamma-chain receptor family, comprising interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21, are vital with respect to organizing and sustaining healthy immune cell functions. Supporting the anticancer immune response, these cytokines inspire great interest for their use as vaccine adjuvants and cancer immunotherapies. It is against this background that gamma delta (gamma delta) T cells, as special-force soldiers and natural contributors of the tumor immunosurveillance, also received a lot of attention the last decade. As gamma delta T cell-based cancer trials are coming of age, this present review focusses on the effects of the different cytokines of the common gamma-chain receptor family on gamma delta T cells with respect to boosting gamma delta T cells as a therapeutic target in cancer immunotherapy. This review also gathers data that IL-15 in particular exhibits key features for augmenting the anti-tumor activity of effector killer gamma delta T cells whilst overcoming the myriad of immune escape mechanisms used by cancer cells.