Raverdeau et al. review the current knowledge of human and murine γδ T cell subsets (particularly tissue-resident γδ1 and blood γ9δ2 T cells), including their pro-tumor functions (induction of angiogenesis, recruitment of immunosuppressive neutrophils, suppression of αβ T cells via expression of checkpoint inhibitors), antitumor functions (direct tumor cell killing; MHC-independent and NKG2D-dependent pathways (among others); indirect effects via the production of IFNγ, TNF, and other cytokines that engage other cell types), and plasticity within the TME. γδ T cells present an attractive potential off-the-shelf cellular immunotherapy.

gammadelta T cells are a small population of mostly tissue-resident lymphocytes, with both innate and adaptive properties. These unique features make them particularly attractive candidates for the development of new cellular therapy targeted against tumor development. Nevertheless, gammadelta T cells may play dual roles in cancer, promoting cancer development on the one hand, while participating in antitumor immunity on the other hand. In mice, gammadelta T-cell subsets preferentially produce IL-17 or IFN-gamma. While antitumor functions of murine gammadelta T cells can be attributed to IFN-gamma(+) gammadelta T cells, recent studies have implicated IL-17(+) gammadelta T cells in tumor growth and metastasis. However, in humans, IL-17-producing gammadelta T cells are rare and most studies have attributed a protective role to gammadelta T cells against cancer. In this review, we will present the current knowledge and most recent findings on gammadelta T-cell functions in mouse models of tumor development and human cancers. We will also discuss their potential as cellular immunotherapy against cancer.

Author Info: (1) School of Biochemistry and Immunology Trinity College Dublin Dublin Ireland. (2) School of Biochemistry and Immunology Trinity College Dublin Dublin Ireland. (3) Harvard Medica

Author Info: (1) School of Biochemistry and Immunology Trinity College Dublin Dublin Ireland. (2) School of Biochemistry and Immunology Trinity College Dublin Dublin Ireland. (3) Harvard Medical School Boston MA USA. Brigham and Women's Hospital Boston MA USA. (4) School of Biochemistry and Immunology Trinity College Dublin Dublin Ireland. Harvard Medical School Boston MA USA. Brigham and Women's Hospital Boston MA USA.