Myeloid-Derived Suppressor Cells Specifically Suppress IFN-γ Production and Antitumor Cytotoxic Activity of Vδ2 T Cells

gamma delta T cells represent less than 5% of circulating T cells; they exert a potent cytotoxic function against tumor or infected cells and secrete cytokines like conventional alpha beta T cells. As alpha beta T cells gamma delta T cells reside in the typical T cell compartments (the lymph nodes and spleen), but are more widely distributed in tissues throughout the body. For these reasons, some investigators are exploring the possibility of immunotherapies aimed to expand and activate V delta 2 T cells, or using them as Chimeric Antigen Receptor carriers. However, the role of immunosuppressive microenvironment on V delta 2 T cells during infections and cancers has not been completely elucidated. In particular, the effects of myeloid-derived suppressor cells (MDSC), largely expanded in such pathologies, were not explored. In the present work, we demonstrated that MDSC may inhibit IFN-gamma production and degranulation of phosphoantigen-activated V delta 2 T cells. Moreover, the V delta 2 T cells cytotoxic activity against the Burkitt lymphoma cell line Daudi and Jurkat cell line were impaired by MDSC. The Arginase I seems to be involved in the impairment of V delta 2 T cell function induced by both tumor cells and MDSC. These data open a key issue in the context of V delta 2-targeted immunoteraphy, suggesting the need of combined strategies aimed to boost V delta 2 T cells circumventing tumor- and MDSC-induced V delta 2 T cells suppression.