Particulate beta-glucan modulates myeloid-derived suppressor cells (MDSC) activity in tumor-bearing mice and lung cancer patients (TUM4P.931)

Abstract

Abstract Whole glucan particles (WGP) are microparticles of 1,3-beta glucan with 1,6-branches purified from the yeast Saccharamyces cerevisiae. Previous studies have reported its therapeutic efficacy in different tumor models through the activation of dendritic cells and macrophages via the c-type lectin receptor dectin-1. In this study, we investigated the effect of WGP treatment on myeloid-derived suppressor cells (MDSC) in mouse tumor models and in patients with non-small cell lung cancer (NSCLC). MDSC are a heterogeneous population of immature myeloid cells with suppressive activity that accumulate in cancer. Here we found that tumor-bearing mice treated orally with WGP have a significantly lower tumor weight with a significant decrease in the percentage of MDSC in the spleen compared to untreated animals in vivo. Patients with NSCLC treated with WGP prior to surgery have a decreased trend in MDSC percentage and increased respiratory burst of neutrophils in the peripheral blood. In addition, in vitro stimulation of MDSC subsets with WGP abrogates STAT3 phosphorylation in polymorphonuclear MDSC and enhances STAT3 phosphorylation in monocytic MDSC, with the activation of Erk1/2 phosphorylation in both subsets, suggesting that WGP differently modulates MDSC subsets. Moreover, MDSC treated with WGP have a decreased suppressive activity when cocultured with OVA-specific OTI and OTII splenocytes. Overall, these data indicate that WGP might be a new modulator of MDSC function in cancer.