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J Immunol. 2016 Mar 1;196(5):2167-80. doi: 10.4049/jimmunol.1501853. Epub 2016 Jan 25.

Yeast-Derived Particulate β-Glucan Treatment Subverts the Suppression of Myeloid-Derived Suppressor Cells (MDSC) by Inducing Polymorphonuclear MDSC Apoptosis and Monocytic MDSC Differentiation to APC in Cancer.

Author information

1
Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202;
2
Division of Hematology and Medical Oncology, Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202; and.
3
Division of Thoracic Surgery, Department of Cardiovascular and Thoracic Surgery, University of Louisville, Louisville, KY 40202.
4
Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202; Division of Hematology and Medical Oncology, Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202; and jun.yan@louisville.edu.

Abstract

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we demonstrated that activation of a C-type lectin receptor, dectin-1, in MDSC differentially modulates the function of different MDSC subsets. Yeast-derived whole β-glucan particles (WGP; a ligand to engage and activate dectin-1, oral treatment in vivo) significantly decreased tumor weight and splenomegaly in tumor-bearing mice with reduced accumulation of polymorphonuclear MDSC but not monocytic MDSC (M-MDSC), and decreased polymorphonuclear MDSC suppression in vitro through the induction of respiratory burst and apoptosis. On a different axis, WGP-treated M-MDSC differentiated into F4/80(+)CD11c(+) cells in vitro that served as potent APC to induce Ag-specific CD4(+) and CD8(+) T cell responses in a dectin-1-dependent manner. Additionally, Erk1/2 phosphorylation was required for the acquisition of APC properties in M-MDSC. Moreover, WGP-treated M-MDSC differentiated into CD11c(+) cells in vivo with high MHC class II expression and induced decreased tumor burden when inoculated s.c. with Lewis lung carcinoma cells. This effect was dependent on the dectin-1 receptor. Strikingly, patients with non-small cell lung carcinoma that had received WGP treatment for 10-14 d prior to any other treatment had a decreased frequency of CD14(-)HLA-DR(-)CD11b(+)CD33(+) MDSC in the peripheral blood. Overall, these data indicate that WGP may be a potent immune modulator of MDSC suppressive function and differentiation in cancer.

PMID:
26810222
PMCID:
PMC4761495
[Available on 2017-03-01]
DOI:
10.4049/jimmunol.1501853
[Indexed for MEDLINE]
Free PMC Article

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