Summary: | 碩士 === 國立臺灣大學 === 生化科技學系 === 105 === 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, which produced higher yields of PS-F2 than the original strain. In both preventive and therapeutic regimens, continuous oral administration of PS-F2 effectively suppressed the growth of colon 26 (CT-26) carcinoma and splenomegaly in tumor-bearing mice without adverse effects on the animals’ health. We found that PS-F2 treatment resulted in augmented cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses, while significantly reduced 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 reduced the accumulation of tumor-associated macrophages (TAMs). In vitro, PS-F2 treatment in bone-marrow derived monocytic-MDSC resulted in elevated levels of maturation and differentiation markers as well as the production of TNF-α and IL-6. Overall, our data demonstrated that oral treatment of PS-F2 from a UV-mutated G. formosanum variant in CT26 tumor-bearing mice activated antitumor immune responses and reduced the accumulation of immunosuppressive cells in the spleen and the tumor, leading to delayed tumor progression. PS-F2 has the potential to be developed as a cancer immunotherapeutic agent.
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