Introduction: Cancer immunotherapy relies on the development of an efficient and long-lasting anti-tumor response, generally mediated by cytotoxic T cells. γδ T cells possess distinctive features that justify their use in cancer immunotherapy. Areas covered: Here we will review our current knowledge on the functions of human γδ T cells that may be relevant in tumor immunity and the most recent advances in our understanding of how these functions are regulated in the tumor microenvironment. We will also discuss the major achievements and limitations of γδ T cell-based immunotherapy of cancer. Expert opinion: Several small-scale clinical trials have been conducted in cancer patients using either in vivo activation of γδ T cells or adoptive transfer of ex vivo-expanded γδ T cells. Both strategies are safe and give some clinical benefit to patients, thus providing a proof of principle for their utilization in addition to conventional therapies. However, low objective response rates have been obtained in both settings and therefore larger and well-controlled trials are needed. Discovering the factors which influence the success of γδ T cell-based immunotherapy will lead to a better understanding of their mechanism of action and to harness these cells for effective and durable anti-tumor responses.
Keywords: adoptive transfer; cancer; cytotoxicity; tumor microenvironment; γδ T cells.