γδ T Cells: Unexpected Regulators of Cancer Development and Progression

Accumulating evidence suggests a role for gamma delta (gamma delta) T cells as unexpected drivers of tumor development and progression. These protumoral gamma delta T cells are abundant in the tumor microenvironment in both mouse and human. They promote tumor progression by: (i) inducing an immunosuppressive tumor microenvironment and angiogenesis via cytokine production; (ii) functioning as regulatory T (Treg)/T helper 2 (Th2)-like cells; (iii) interfering with dendritic cell (DC) effector function; and (iv) inhibiting antitumor adaptive T cell immunity via the programmed death-1 (PD-1)-programmed death ligand-1 (PD-L1) pathway. Understanding how these cells are regulated and what their specific role in cancer is will provide insight for the development of approaches that specifically target these cells and can thereby improve the efficacy of cancer immunotherapies.