Ganoderma formosanum polysaccharides enhance antitumor immune responses by downregulating the differentiation of myeloid-derived suppressor cells and tumor-associated macrophages

Ganoderma formosanum is a native species of Ganoderma isolated in Taiwan, and our previous studies showed that a polysaccharide fraction, PS-F2, purified from the submerged culture fluid of G. formosanum ATCC 76538 exhibited immunostimulatory and antitumor property. In the current study, we investigated the immunomodulatory and antitumor effects of PS-F2 from a UV-mutated G. formosanum variant NTU-1, which produced higher yields of PS-F2 than the original strain. Oral administration of PS-F2 effectively suppressed the growth of colon 26 (CT-26) carcinoma and splenomegaly in tumor-bearing mice without adversely affecting the animals health. We found that PS-F2 treatment resulted in augmented cytotoxic T lymphocyte (CTL) while significantly reducing the accumulation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and regulatory T (Treg) cells in the spleen. In the tumor, PS-F2 treatment markedly enhanced CTL and Th1 responses, whereas it reduced the accumulation of tumor-associated macrophages (TAMs). Collectively, our data demonstrate that oral treatment of PS-F2 from G. formosanum NTU-1 in CT26 tumor-bearing mice activates antitumor immune responses and reduces the accumulation of immunosuppressive cells in the spleen and the tumor, leading to delayed tumor progression.