Complex role of γδ T-cell-derived cytokines and growth factors in cancer.

γδ T cells are innate lymphocytes that recognize and kill a range of tumor cells and are currently being explored as a target for tumor immunotherapy. However, γδ T cells play a complex role in cancer and can promote, as well as inhibit, tumor growth. In addition to tumor cell killing, γδ T cells express a number of cytokines and other soluble factors in response to tumors. Soluble factors expressed by γδ T cells in these settings include interferon-γ, tumor necrosis factor-α, interleukin (IL)-4, IL-10, transforming growth factor-β, IL-17, and a number of growth factors. These factors have differing and sometimes opposing effects on antitumor immunity and tumor angiogenesis, and likely contribute to the complex role of these cells in cancer. Here, we review studies in both mice and humans that examine differential cytokine secretion by γδ T cells in response to tumors and tumor immunotherapy, and discuss the influence of these γδ T-cell-derived factors on tumor growth.