A novel polysaccharide isolated from Coriolus versicolor polarizes M2 macrophages into an M1 phenotype and reversesits immunosuppressive effect on tumor microenvironment

Abstract

Converting M2 macrophages into an M1 phenotype in the tumor microenvironment, provides a new direction for tumor treatment. Here, we further report CVPW-1, a new polysaccharide of 1.03 × 106 Da that was isolated from Coriolus versicolor. Its monosaccharide was composed of mannose, glucose, and galactose at a ratio of 1.00:8.73:1.68. The backbone of CVPW-1 was composed of (1 → 3)-linked α-D-Glcp residues and (1 → 3,6)-linked α-D-Glcp residues that branched at O-6. The branch consisted of (1 → 6)-linked α-D-Glcp residues and (1 → 4)-linked α-D-Glap, and some branches were terminated with (1→)-linked β-D-Manp residues according to the results of HPLC, FT-IR, GC–MS, 1D and 2D NMR. Meanwhile, CVPW-1 could polarize M2 macrophages to M1 phenotypein vitro by binding to TLR4 and inducing the activation of Akt, JNK and NF-κB. This process involved reversing the functional inhibition of CD8+ T lymphocytes by inhibiting the expression of TREM2 in M2 macrophages. The in vivo experiments showed that oral administration of CVPW-1 could inhibit the growth of tumor in mice and polarize TAMs to M1 phenotype. Thus, the novel polysaccharide CVPW-1 from Coriolus versicolor might activate a variety of immune cells and then play an anti-tumor role. These results demonstrated that CVPW-1 could be developed as a potential immuno-oncology treatment reagent.