The emerging protumor role of γδ T lymphocytes: Implications for cancer immunotherapy

Abstract

Tumor-infiltrating lymphocytes are key mediators of tumor immune surveillance and are important prognostic indicators in cancer progression. Among the various lymphocyte subsets implicated in protection against cancer are γδ T lymphocytes, which can kill tumor cells and secrete potent antitumor cytokines. By contrast, recent reports have revealed an unexpected series of protumor functions of γδ T cells in mouse models and human patients. In particular, specific γδ T-cell subsets are capable of recruiting immunosuppressive myeloid populations, inhibiting antitumor responses, and enhancing angiogenesis, thus promoting cancer progression. A common mediator of such functions appears to be the cytokine IL17, whose pathogenic effects can override the antitumor immune response orchestrated by IFNγ. Here, we review these studies and discuss their implications for the manipulation of γδ T cells in cancer immunotherapy.