Pro-tumor γδ T Cells in Human Cancer: Polarization, Mechanisms of Action, and Implications for Therapy

The tumor immune microenvironment contributes to tumor initiation, progression and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of γ and δ chains (γδ T cells) are of particular interest. Indeed, γδ T cells contribute to the immune response against many cancers, notably through their powerful effector functions that lead to the elimination of tumor cells and the recruitment of other immune cells. However, their presence in the tumor microenvironment has been associated with poor prognosis in various solid cancers (breast, colon and pancreatic cancer), suggesting that γδ T cells also display pro-tumor activities. In this review, we outline the current evidences of γδ T cell pro-tumor functions in human cancer. We also discuss the factors that favor γδ T cell polarization toward a pro-tumoral phenotype, the characteristics and functions of such cells, and the impact of pro-tumor subsets on γδ T cell-based therapies.