Maitake ?-glucan promotes differentiation of monocytic myeloid-derived suppressor cells into M1 macrophages

Aims: Myeloid-derived suppressor cells (MDSCs) are major components of the tumor microenvironment and systemically accumulate in tumor-bearing hosts and patients with cancer, facilitating cancer progression. Mai -take macromolecular alpha-glucan YM-2A, isolated from Grifola frondosa, inhibits tumor growth by enhancing im-mune responses. The present study investigated the effects of YM-2A on the immunosuppressive potential of MDSCs. Main methods: YM-2A was orally administered to CT26 tumor-bearing mice, and the number of immune cells in the spleen and tumor was measured. Splenic MDSCs isolated from the CT26 tumor-bearing mice were treated with YM-2A and co-cultured with T cells to measure their inhibitory effect on T cell proliferation. For adoptive transfer of monocytic MDSCs (M-MDSCs), YM-2A-treated M-MDSCs mixed with CT26 cells were implanted subcutaneously in the mice to measure the tumor growth rate.Key findings: YM-2A selectively reduced the accumulation of M-MDSCs but not that of polymorphonuclear MDSCs (PMN-MDSCs) in CT26 tumor-bearing mice. In tumor tissues, YM-2A treatment induced the polarity of immu-nostimulatory M1-phenotype; furthermore, it increased the infiltration of dendritic, natural killer, and CD4+ and CD8+ T cells. YM-2A treatment of purified M-MDSCs from CT-26 tumor-bearing mice induced dectin-1-dependent differentiation into M1 macrophages. YM-2A-treated M-MDSCs lost their inhibitory activity against proliferation and activation of CD8+ T cells. Furthermore, adoptive transfer of M-MDSCs treated with YM-2A inhibited CT26 tumor growth.Significance: YM-2A promotes the differentiation of M-MDSCs into immunostimulatory M1 macrophages, thereby enhancing the efficacy of cancer immunotherapy.

Automated summary

This study investigated the effects of YM-2A, a compound extracted from Grifola frondosa, on the immunosuppressive potential of MDSCs. The results showed that YM-2A selectively reduced the accumulation of M-MDSCs in tumor-bearing mice and promoted the differentiation of M-MDSCs into immunostimulatory M1 macrophages, thus enhancing the efficacy of cancer immunotherapy.