Deciphering human gd T cell response in cancer: Lessons from tumor-infiltrating gd T cells

The finding that gd T cells are present among tumor-infiltrating lymphocytes in humans suggests they participate in tumor immune surveillance, but their relevance is unclear because the relative abundance of tumor gdT cells correlates with positive or negative, or even do not correlate with prognosis. This likely depends on the fact that tumor-infiltrating gd T cells may play substantially different effector or regulatory functions, and correlation with patient's prognosis relies on distinct gd T cell subsets in the context of the tumor. There is interest to exploit gd T cells in tumor immunotherapy, but to make this approach successful there is urgent need to fully understand the biological functions of gd T cells and of how they can be manipulated in vivo and ex vivo to safely provide benefit to the host. This review focuses on our previous and ongoing studies of tumor-infiltrating gd T lymphocytes in different types of human cancer. Moreover, we discuss the interaction of tumor-infiltrating gd T cells with other cells and molecules present in the tumor microenvironment, and their clinical relevance on the ground, that deep knowledge in this field can be used further for better immunotherapeutic intervention in cancer.