Galactan isolated from Cantharellus cibarius modulates antitumor immune response by converting tumor-associated macrophages toward M1-like phenotype

Tumor-associated Macrophages (TAMs) with an M2-like phenotype have been linked to the proliferation, invasion and metastasis of tumor cells. Resetting tumor-associated Macrophages represents an attractive target for an effective Cancer Immunotherapy. WCCP-N-b, a novel linear 3-O-methylated galactan, isolated from Cantharellus cibarius, can convert tumor-promoting M2-like Macrophages to tumor-inhibiting M1-like phenotype. On a cellular mechanistic level, WCCP-N-b inhibited M2-like Macrophages polarization through suppression of STAT6 activation. Furthermore, WCCP-N-b increased the phosphorylation of mitogen-activated protein Kinases (MAPKs) and degradation of IκB-α through targeting Toll-like Receptor 2 (TLR2). The activation of MAPKs and degradation of IκB-α were responsible for converting M2-like Macrophages to M1-like Macrophages. Importantly, Cell Culture supernatants of WCCP-N-b-treated M2-like Macrophages could inhibit the cell viability of B16F1 and B16F10. Our findings provide a potential natural and harmless polysaccharide for macrophage-based tumor immunotherapy.