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.

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.

Hampering immune suppressors: therapeutic targeting of myeloid-derived suppressor cells in cancer.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with suppressive properties that preferentially expand in cancer. Myeloid-derived suppressor cells mainly suppress T-cell proliferation and cytotoxicity, inhibit natural killer cell activation, and induce the differentiation and expansion of regulatory T cells. The wide spectrum of MDSC suppressive activity in cancer and its role in tumor progression have rendered these cells a promising target for effective cancer immunotherapy.

The effects of β-glucans on dendritic cells and implications for cancer therapy.

β-Glucans are polysaccharides of β-D-glucose extracted from the cell walls of different species of mushrooms, yeast, oat, barley, seaweeds, algae and bacteria. Modern biomedical research has identified β-glucans as biological response modifiers (BRM) with anti-tumor properties that elicit potent immune responses through their recognition by a variety of pattern recognition receptors (PRRs) on dendritic cells (DCs), macrophages and neutrophils. Complement receptor-3 (CR3), lactosylceramides, scavenger receptors and dectin-1 are involved in β-glucan recognition, triggering a series of signaling events that modulate innate and subsequently adaptive immune responses.