Polysaccharide from Lentinus edodes Inhibits the Immunosuppressive Function of Myeloid-Derived Suppressor Cells |
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Authors: | Hao Wu Ning Tao Xiaoman Liu Xiao Li Jian Tang Chungwah Ma Xiaofei Xu Haitao Shao Baidong Hou Hui Wang Zhihai Qin |
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Institution: | 1. Xinxiang Medical University, Xinxiang, China.; 2. Protein and Peptide Pharmaceutical Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.; 3. Infinitus (China) Company Ltd., Guangzhou, China.; 4. Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.; Instituto Butantan, Brazil, |
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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. |
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