The Ambiguous Role of γδ T Lymphocytes in Antitumor Immunity

gamma delta T cells play a role in immune surveillance because they recognize stress-induced surface molecules and metabolic intermediates that are frequently dysregulated in transformed cells. Hence, gamma delta T cells have attracted much interest as effector cells in cell-based immunotherapy. Recently, however, it has been realized that gamma delta T cells can also promote tumorigenesis through various mechanisms including regulatory activity and IL-17 production. In this review we outline both the pathways involved in cancer cell recognition and killing by gamma delta T cells as well as current evidence for their protumorigenic activity in various models. Finally, we discuss strategies to improve the tumor reactivity of gamma delta T cells and to counteract their protumorigenic activities, which should open improved perspectives for their clinical application.