The Emerging Protumor Role of γδ T Lymphocytes: Implications for Cancer Immunotherapy

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 gamma delta 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 gamma delta T cells in mouse models and human patients. In particular, specific gamma delta 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 IFN gamma. Here, we review these studies and discuss their implications for the manipulation of gamma delta T cells in cancer immunotherapy.