γδ T cells in cancer immunotherapy: current status and future prospects

Abstract

γδ T lymphocytes are a distinct T-cell subset that display unique features with respect to T-cell receptor (TCR) gene usage, tissue tropism and antigen recognition. Phosphoantigens contributed by a dysregulated mevalonate pathway or the bacterial nonmevalonate pathway and aminobisphosphonates are capable of activating Vγ9Vδ2 T cells. With the aid of synthetic phosphoantigens, large-scale expansion of γδ T cells and their adoptive transfer into human hosts is now possible. The present review summarizes triumphs and tribulations of clinical trials using γδ T-cell immunotherapy. Adoptive transfer of phosphoantigen-activated γδ T cells or coadministration with aminobisphosphonates/cytokines/monoclonal antibodies appear to be promising approaches for cancer immunotherapy. It can be predicted that a comprehensive understanding of the molecular interactions of this unique T-cell subset with other key immune regulators (dendritic cells and regulatory T cells) will provide an impetus to bring this modality of treatment from bench to bedside.