Polysaccharide From Lentinus Edodes Induce The Differentiation Of Myeloid-Derived Suppressor Cells

Back GroundMDSCs were a group of immature cells composed by two main subsets, Monocytic MDSCs and Granulocytic MDSCs. They can help tumor cells escape from immune system by inhibiting the cytotoxicity and proliferation of T cells and NK cells, or promoting the vascular growth in tumor cite. Reversing the function of immune suppressor cells may improve the efficacy of cancer therapy. Here, we have isolated a novel polysaccharide MPSSS (577.2Kd) from Lentinus edodes and examined its effects on differentiation and function of myeloid-derived suppressor cells (MDSCs).ObjectiveTo observe if MPSSS could influence the differentiation and function of MDSCs.Methods1. Ethanol precipitation technique was used to get the polysaccharide MPSSS, size-exclusion chromatography was used to detect the molecular weight and purity of MPSSS, HPLC was used to check the compose of MPSSS, NMR was used to detect the structure of MPSSS.2. To generate tumor models, McgR32tumor cells were injected subcutaneously in the flank of C57BL/6and MyD88-/-mice.3. BD FACSAria was used to isolate MDSCs from spleen of tumor-bearing mice.4. Flow cytometry was used to detect the expression of MHCⅡ, F4/80, CDllc, and CD86.5.3H label technology was used to detect the proliferation of T cells.6. Immunohistochemical technology was used to check the level of F4/80on MDSCs.7. The mRNA level of CXCL9/IL-6/TGF-β/TLR2/TLR4/TLR9were detected by Real-time PCR.8. Western Blot was used to detect the activation of NF-κB signal pathway. Result1. Purification of Compounds from L. edodes Polysaccharides by Ethanol precipitation technique.2. MPSSS Inhibited Tumor Growth in vivo.3. MPSSS Promoted Differentiation of MDSCs.4. MPSSS Eliminated the MDSC-mediated T cell Inhibition.5. MPSSS Activated Ly6Chigh CD11b+Cells but not Ly6Cint CD11b+Cells.6. MPSSS Activated the MyD88-dependent NF-kB signal pathway in MDSCs.ConclusionMPSSS, a polysaccharide from L. edodes, induced the differentiation of MDSCs, reversed their immune suppressor functions and therefore inhibited tumor growth.