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.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Animals
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CD11c Antigen / genetics
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CD11c Antigen / immunology
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Carcinoma, Lewis Lung / drug therapy*
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Carcinoma, Lewis Lung / genetics
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Carcinoma, Lewis Lung / immunology*
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Carcinoma, Lewis Lung / pathology
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Cell Differentiation / drug effects*
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Cell Movement / drug effects
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / pathology
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Fungal Polysaccharides / isolation & purification
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Fungal Polysaccharides / pharmacology*
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Gene Expression Regulation, Neoplastic / drug effects
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Immunologic Factors / isolation & purification
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Immunologic Factors / pharmacology*
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Immunosuppression Therapy
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Macrophages / drug effects
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Macrophages / immunology
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Macrophages / pathology
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Mice
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Myeloid Cells / drug effects*
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Myeloid Cells / immunology
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Myeloid Cells / pathology
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NF-kappa B / genetics
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NF-kappa B / immunology
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Saccharomyces cerevisiae / chemistry
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Spleen / drug effects
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Spleen / immunology
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Spleen / pathology
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / pathology
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / pathology
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beta-Glucans / isolation & purification
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beta-Glucans / pharmacology*
Substances
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CD11c Antigen
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Fungal Polysaccharides
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Immunologic Factors
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Lectins, C-Type
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NF-kappa B
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beta-Glucans
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dectin 1