Gamma delta (γδ) T cells in cancer immunotherapy; where it comes from, where it will go?

Cancer immunotherapy is a field of interest in the recent treatment approaches against cancer cells, as it could use the assets of the host's immune system against the invading tumor cells. In cancer immunotherapy, for a while, αβT cells play fundamental roles; however, their dependence on major histocompatibility complex (MHC), their ability to only recognize mutated peptides, as well as their low tropism to the tumor sites, especially in solid tumors, have put an obstacle on their way into the clinical settings. Currently, a renewed interest has focused on γδT cells -cells that act as a bridge between the innate and adaptive arm of the immune system- in cancer immunotherapy. γδT cells have been shown to induce anti-tumor effects in cancer cells, but not in normal cells. Their genetic structure also allows easy manipulation for therapeutic interventions. γδT cells could recognize a wide range of antigens, such as lipids, phospho-antigens, and peptides, in MHC-dependent and -independent manner; suggesting that these cells could also exert anti-tumor effects against tumors with low mutational burdens and downregulated MHC. Although seems promising, it should not be forgotten that the application of γδT cells in cancer research is relatively at its infancy and many challenges and hurdles are yet to be identified. In the present review, we discuss the advantages as well as the challenges of γδT cells-based immunotherapies in human cancer and propose how new technologies could solve these limitations.