Harnessing the potential of the medicinal fungus Innonotus obliquus to induce tumoricidal macrophages

Macrophages are essential innate immune cells which have increasingly become attractive manipulable targets in designing therapies, given their significant involvement in the pathophysiology of several diseases, including cancers. In the microenvironment of solid tumors, tumor associated macrophages (TAMs), either promote or suppress tumor growth depending on activating cues from the tumor milieu. Both in vitro and in vivo studies have recently identified fungal polysaccharides as potent macrophage activators capable of stimulating TAMs into tumoricidal phenotypes. In this study, an optimized protocol for generating human macrophages from peripheral blood monocytes in vitro using Granulocyte macrophage colony stimulating factor (G-MCSF) or macrophage colony stimulating factor (M-CSF) was established. Fungal polysaccharides isolated from the medicinal fungus, Inonotus obliquus, stimulated human macrophages in vitro to secrete the pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-12p70, essential for a complete anti-tumor immune response. Next, we showed that murine bone marrow-derived macrophages activated with the fungal polysaccharides induced an anti-tumor response against cancer in mouse models. This study shows that the novel fungal polysaccharides from I. obliquus play a significant role in activating an anti-tumor phenotype in macrophages and could be exploited as a potentially effective candidate for cancer immunotherapy