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

Int J Biol Macromol. 2024 Feb;259(Pt 2):129352. doi: 10.1016/j.ijbiomac.2024.129352. Epub 2024 Jan 11.

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.

PMID:38218293 | DOI:10.1016/j.ijbiomac.2024.129352