Human γδ T Cell Subsets and Their Clinical Applications for Cancer Immunotherapy

SIMPLE SUMMARY: Research into the immunotherapeutic potential of T cells has predominantly focused on conventional alpha beta (αβ) T cells, which recognize peptide antigens presented by polymorphic major histocompatibility complex (MHC) class I and class II molecules. However, innate-like T cells, such as gamma delta (γδ) T cells, also play important roles in antitumor immunity. Here, we review the current understanding of γδ T cells in antitumor immunity and discuss strategies that could potentially maximize their potential in cancer immunotherapy. ABSTRACT: Gamma delta (γδ) T cells are a minor population of T cells that share adaptive and innate immune properties. In contrast to MHC-restricted alpha beta (αβ) T cells, γδ T cells are activated in an MHC-independent manner, making them ideal candidates for developing allogeneic, off-the-shelf cell-based immunotherapies. As the field of cancer immunotherapy progresses rapidly, different subsets of γδ T cells have been explored. In addition, γδ T cells can be engineered using different gene editing technologies that augment their tumor recognition abilities and antitumor functions. In this review, we outline the unique features of different subsets of human γδ T cells and their antitumor properties. We also summarize the past and the ongoing pre-clinical studies and clinical trials utilizing γδ T cell-based cancer immunotherapy.