Promoting angiogenesis within the tumor microenvironment: The secret life of murine lymphoid IL-17-producing γδ T cells

After two decades in the shadow of their all counterparts, gamma delta T cells have recently gathered significant attention following the discovery that they produce IL-17 in various mouse models of infection and autoimmune disease. In contrast, the secretion of large amounts of IFN-gamma by gamma delta T cells has long been known, and has been tightly linked to their anti-tumor function. In this issue of the European Journal of Immunology, a study unexpectedly reports that the lymphoid gamma delta T cells that infiltrate tumor foci induced in the mouse skin produce very little IFN-gamma, but abundant IL-17. In fact, these gamma delta T cells are the major source of IL-17 within the tumor microenvironment, where they appear to promote angiogenesis, and thus tumor growth. This Commentary discusses the relevance of these interesting findings in the context of the currently paradoxical pro- versus anti-tumor roles of IL-17 in cancer immunology.