Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Ly / metabolism
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Antineoplastic Agents / pharmacology
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CD11b Antigen / metabolism
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Cell Differentiation / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Disease Models, Animal
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Fungal Polysaccharides / chemistry
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Fungal Polysaccharides / isolation & purification
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Fungal Polysaccharides / pharmacology*
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Humans
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / isolation & purification
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Immunosuppressive Agents / pharmacology*
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Mice
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Myeloid Cells / cytology
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Myeloid Cells / drug effects*
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Myeloid Cells / immunology*
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Myeloid Cells / metabolism
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Myeloid Differentiation Factor 88 / metabolism
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NF-kappa B / metabolism
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Neoplasms / immunology
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Neoplasms / pathology
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Shiitake Mushrooms / chemistry*
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Signal Transduction
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T-Lymphocytes / immunology
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Tumor Burden / drug effects
Substances
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Antigens, Ly
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Antineoplastic Agents
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CD11b Antigen
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Fungal Polysaccharides
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Immunosuppressive Agents
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Ly-6C antigen, mouse
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Myeloid Differentiation Factor 88
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NF-kappa B
Grants and funding
This project was supported by Plan for Scientific Innovation Talent of Henan Province (104200510001), and the National Natural Science Foundation of China (31071261). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.