Polysaccharide from Lentinus edodes inhibits the immunosuppressive function of myeloid-derived suppressor cells

• Published in: PloS one 2012-12, Vol.7 (12), p.e51751-e51751
• Main Authors: Wu, Hao, Tao, Ning, Liu, Xiaoman, Li, Xiao, Tang, Jian, Ma, Chungwah, Xu, Xiaofei, Shao, Haitao, Hou, Baidong, Wang, Hui, Qin, Zhihai
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Ly - metabolism; Antineoplastic Agents - pharmacology; Biology; Biophysics; Cancer; Cancer treatment; CD11b Antigen - metabolism; CD4 antigen; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Chromatography; Cytokines; Development and progression; Differentiation; Disease Models, Animal; Flow cytometry; Fungal Polysaccharides - chemistry; Fungal Polysaccharides - isolation & purification; Fungal Polysaccharides - pharmacology; Galactose; Gene expression; Health aspects; Humans; Immunosuppression; Immunosuppressive agents; Immunosuppressive Agents - chemistry; Immunosuppressive Agents - isolation & purification; Immunosuppressive Agents - pharmacology; Laboratories; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Mannose; Medicine; Mice; Molecular weight; Monosaccharides; Morphology; MyD88 protein; Myeloid Cells - cytology; Myeloid Cells - drug effects; Myeloid Cells - immunology; Myeloid Cells - metabolism; Myeloid Differentiation Factor 88 - metabolism; Neoplasms - immunology; Neoplasms - pathology; NF-kappa B - metabolism; NF-κB protein; Peptides; Peripheral blood; Pharmaceuticals; Polysaccharides; Proteins; Rodents; Shedding; Shiitake Mushrooms - chemistry; Signal Transduction; Signaling; Suppressor cells; T cells; T-Lymphocytes - immunology; Tumor Burden - drug effects; Tumor cells; Tumors; Xylose
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0051751

Reversing the function of immune suppressor cells may improve the efficacy of cancer therapy. Here, we have isolated a novel polysaccharide MPSSS (577.2 Kd) from Lentinus edodes and examined its effects on differentiation and function of myeloid-derived suppressor cells (MDSCs). MPSSS is composed of glucose (75.0%), galactose (11.7%), mannose (7.8%), and xylose (0.4%). In vivo, it inhibits the growth of McgR32 tumor cells, which is correlated with a reduced percentage of MDSCs in peripheral blood. In vitro, it induces both morphological and biophysical changes in MDSCs. Importantly, MPSSS up-regulates MHC II and F4/80 expression on MDSCs, and reverses their inhibition effect on CD4(+) T cells in a dose-dependent manner. The mechanism study shows that MPSSS may stimulate MDSCs through a MyD88 dependent NF-κB signaling pathway. Together, we demonstrated for the first time that MPSSS stimulates the differentiation of MDSCs and reverses its immunosuppressive functions, shedding new light on developing novel anti-cancer strategies by targeting MDSCs.