β-Glucan enhances antitumor immune responses by regulating differentiation and function of monocytic myeloid-derived suppressor cells

Eur J Immunol. 2013 May;43(5):1220-30. doi: 10.1002/eji.201242841. Epub 2013 Mar 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • CD11c Antigen / genetics
  • CD11c Antigen / immunology
  • Carcinoma, Lewis Lung / drug therapy*
  • Carcinoma, Lewis Lung / genetics
  • Carcinoma, Lewis Lung / immunology*
  • Carcinoma, Lewis Lung / pathology
  • Cell Differentiation / drug effects*
  • Cell Movement / drug effects
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Fungal Polysaccharides / isolation & purification
  • Fungal Polysaccharides / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Immunologic Factors / isolation & purification
  • Immunologic Factors / pharmacology*
  • Immunosuppression
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / pathology
  • Mice
  • Myeloid Cells / drug effects*
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Saccharomyces cerevisiae / chemistry
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology
  • beta-Glucans / isolation & purification
  • beta-Glucans / pharmacology*

Substances

  • CD11c Antigen
  • Fungal Polysaccharides
  • Immunologic Factors
  • Lectins, C-Type
  • NF-kappa B
  • beta-Glucans
  • dectin 1