Accumulation of myeloid-derived suppressor cells (MDSCs) induced by low levels of IL-6 correlates with poor prognosis in bladder cancer

Bladder cancer (BC) is one of the most commonly occurring cancers, with a high recurrence rate and poor outcomes in cases of relapsed metastatic disease. Here, we analyzed the markers and significance of myeloid-derived suppressor cells (MDSCs) for BC development and progression. MDSC markers were examined in peripheral blood from 113 BC patients and 20 healthy volunteers. We identified CD11b(+)CD33(low)HLA-DR- CD3(-) cells as markers of MDSCs in peripheral blood from BC patients. We also demonstrated that MDSC numbers are higher in BC patients than healthy donors, and that MDSC numbers correlate with the clinical grade, stage, and poor prognosis. In addition, serum IL-6 levels are decreased in BC patients with higher MDSC counts. IL-6 blockade increases induction of MDSCs in vitro. Low IL-6 levels inhibit activation of Stat3, resulting in the increased formation of MDSCs in BC. These results indicate that the MDSCs numbers may serve as a novel prognostic marker in BC patients, and that targeting IL-6 signaling may be a promising strategy for BC treatment.