Function of γδ T cells in tumor immunology and their application to cancer therapy

Cancer: T cell subset could boost immunotherapy An under-researched subset of T cells may find application in cancer immunotherapy once their multiple roles are fully understood. Jang Hyun Park and Heung Kyu Lee at the Korea Advanced Institute of Science and Technology, Daejeon, South Korea, have reviewed the current understanding of gamma delta (gamma delta) T cells, which are found in peripheral blood and specific tissues, for example, the skin. They form part of the immune response, but instead of recognizing antigens presented by MHC molecule as do other T cells, they respond to markers of cellular stress during events such as tumorigenesis. Evidence suggests gamma delta T cells play different roles in the tumor microenvironment depending on the proteins they produce and can induce anti-tumor or pro-tumor activity. The authors suggest that harnessing the anti-tumor properties of gamma delta T cells for use in immunotherapy could transform cancer treatments. T cells of the gamma delta lineage are unconventional T cells with functions not restricted to MHC-mediated antigen presentation. Because of their broad antigen specificity and NK-like cytotoxicity, gamma delta T-cell importance in tumor immunology has been emphasized. However, some gamma delta T-cell subsets, especially those expressing IL-17, are immunosuppressive or tumor-promoting cells. Their cytokine profile and cytotoxicity are seemingly determined by cross-talk with microenvironment components, not by the gamma delta TCR chain. Furthermore, much about the TCR antigen of gamma delta T cells remains unknown compared with the extreme diversity of their TCR chain pairs. Thus, the investigation and application of gamma delta T cells have been relatively difficult. Nevertheless, gamma delta T cells remain attractive targets for antitumor therapy because of their independence from MHC molecules. Because tumor cells have the ability to evade the immune system through MHC shedding, heterogeneous antigens, and low antigen spreading, MHC-independent gamma delta T cells represent good alternative targets for immunotherapy. Therefore, many approaches to using gamma delta T cells for antitumor therapy have been attempted, including induction of endogenous gamma delta T cell activation, adoptive transfer of expanded cells ex vivo, and utilization of chimeric antigen receptor (CAR)-T cells. Here, we discuss the function of gamma delta T cells in tumor immunology and their application to cancer therapy.