Modulation of myeloid derived suppressor cells (MDSCs) functions: a new strategy towards hydrogen sulfide anti-cancer effects.

BACKGROUND AND PURPOSE: Myeloid-derived suppressor cells (MDSCs) represent the major obstacle to cancer treatment. In fact, MDSCs negatively regulate antitumor immunity through the suppression of tumor-specific T lymphocytes. Thus, the efficacy of immunotherapies may be improved by targeting MDSCs. In this study, we investigated on the ability of hydrogen sulfide (H2 S), a gasotransmitter whose anti-cancer effects are well-known, to inhibit MDSCs accumulation and immunosuppressive functions in melanoma. EXPERIMENTAL APPROACH: The effect of H2 S on the host immune response to cancer was evaluated using an in vivo syngeneic model of murine melanoma. B16F10-melanoma-bearing mice were treated with diallyl trisulfide (DATS) and analyzed for immune cells composition in relation to MDSCs, dendritic cells (DCs) and T-cells. Moreover, we evaluated H2 S effect on MDSCs immunosuppressive genes expression and on T-cell proliferation. KEY RESULTS: In melanoma-bearing mice, DATS inhibited tumor growth and this effect was associated with a reduction in the frequency of MDSCs in the spleen, in the blood as well as in the tumor microenvironment. In addition, we found that CD8+ T cells and DCs were increased. Furthermore, DATS reduced MDSCs immune suppressive activity restoring T cells proliferation. CONCLUSION AND IMPLICATIONS: This study demonstrate that DATS inhibits the expansion and the suppressive functions of MDSCs, suggesting a novel role for H2 S in the modulation of MDSCs in cancer. Therefore, H2 S-donors may provide a novel approach for enhancing the efficacy of melanoma immunotherapy