title: Polysaccharide from Lentinus edodes inhibits the immunosuppressive function of myeloid-derived suppressor cells.
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.
authors.affiliation: Xinxiang Medical University, Xinxiang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Ning
authors.initials: N
authors.lastname: Tao
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Tang
authors.forename: Chungwah
authors.initials: C
authors.lastname: Ma
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Xu
authors.forename: Haitao
authors.initials: H
authors.lastname: Shao
authors.forename: Baidong
authors.initials: B
authors.lastname: Hou
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D062610:Fungal Polysaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D020942:Shiitake Mushrooms / Q000737:chemistry*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000950:Antigens, Ly; D000970:Antineoplastic Agents; D039481:CD11b Antigen; D062610:Fungal Polysaccharides; D007166:Immunosuppressive Agents; C494192:Ly-6C antigen, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B