title: β-Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid-derived suppressor cells.
abstract: Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a major role in tumor-induced immunosuppression, which hampers effective immuno-therapeutic approaches. β-Glucans have been reported to function as potent immuno-modulators to stimulate innate and adaptive immune responses, which contributes to their antitumor property. Here, we investigated the effect of particulate β-glucans on MDSCs and found that β-glucan treatment could promote the differentiation of M-MDSCs (monocytic MDSCs) into a more mature CD11c(+) F4/80(+) Ly6C(low) population via dectin-1 pathway in vitro, which is NF-κB dependent, and the suppressive function of M-MDSCs was significantly decreased. Treatment of orally administered yeast-derived particulate β-glucan drastically downregulated MDSCs but increased the infiltrated DCs and macrophages in tumor-bearing mice, thus eliciting CTL and Th1 responses, inhibiting the suppressive activity of regulatory T cells, thereby leading to the delayed tumor progression. We show here for the first time that β-glucans induce the differentiation of MDSCs and inhibit the regulatory function of MDSCs, therefore revealing a novel mechanism for β-glucans in immunotherapy and suggesting their potential clinical benefit.
authors: Department of Laboratory Medicine, The Affiliated People's Hospital, Jiangsu University School of Medical Science and Laboratory Medicine, Zhenjiang, China.
authors: Jie
authors: J
authors: Tian
authors: Jie
authors: J
authors: Ma
authors: Ke
authors: K
authors: Ma
authors: Hongye
authors: H
authors: Guo
authors: Samuel Essien
authors: SE
authors: Baidoo
authors: Yue
authors: Y
authors: Zhang
authors: Jun
authors: J
authors: Yan
authors: Liwei
authors: L
authors: Lu
authors: Huaxi
authors: H
authors: Xu
authors: Shengjun
authors: S
authors: Wang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D062610:Fungal Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D047071:beta-Glucans / Q000302:isolation & purification / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D039521:CD11c Antigen; D062610:Fungal Polysaccharides; D007155:Immunologic Factors; D037181:Lectins, C-Type; D016328:NF-kappa B; D047071:beta-Glucans; D000099181:Dectin-1