Juglone eliminates MDSCs accumulation and enhances antitumor immunity

Myeloid-derived suppressor cells (MDSCs) contribute to immune activity suppression and promote the tumor progression. Elimination of MDSCs is a promising cancer therapeutic strategy, and some chemotherapeutic agents have been reported to hamper tumor progression by suppressing MDSCs. Juglone has been showed to exert a direct cytotoxic effect on tumor cells. However, the effect of juglone on MDSCs and anti-tumor immune statue has remained unexplored. In our study, we observed that juglone suppressed tumor growth and metastasis markedly, and the tumor growth suppression in immunocompetent mice was more drastic than that in immunodeficient mice. Juglone reduced the accumulation of MDSCs and increased IFN-gamma production by CD8(+) T cells. Consistently, juglone affected myeloid cells differentiation and maturation, impairing the immunosuppressive functions of MDSCs. Moreover, juglone down-regulated the level of IL-1 beta which was mediating accumulation of MDSCs. In addition, juglone inhibited 5FU-induced liver injury in a colorectal carcinoma bearing mice model. Thus, our work suggests that the anti-tumor effect of juglone is mediated, at least in part, by eliminating accumulation of MDSCs.