IL-17 inhibits the accumulation of myeloid-derived suppressor cells in breast cancer via activating STAT3.

Breast cancer (BC) is one of the most common cancers, with high recurrence rate and poor prognosis of recurrent metastatic disease. In our study, we analyzed the markers and development of markers of myeloid-derived suppressor cells (MDSCs) for BC progression and occurrence. MDSCs is one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. Interleukin-17 (IL-17) is a signature cytokine of Th17 cells. Previous research has indicated that IL-17 plays a proinflammatory role. It was found to increase frequencies at certain tumors and involved in angiogenesis. This study aims to elucidate the biological role of IL-17 on MDSC in BC cells. Expression of MDSC in peripheral blood of 80 BCE patients and 20 healthy volunteers was compared. Our results indicate that MDSC numbers in patients with BC were higher than healthy donors. Moreover, the clinical grade and prognosis were correlate with the number of MDSC. In this study, we investigated the effect of IL-17 on MDSCs. CCK-8 assay and flow cytometry were used to assess the proliferation and apoptosis of cells. The expression of key MDSC-related molecules was detected by western blotting. We identified administration with IL-17 in vitro significantly induced MDSC differentiation, inhibited their proliferation and triggered apoptosis. In addition, Low IL-17 inhibited the activation of STAT3, leading to increase formation of MDSCs in BC. Our results from experiments suggest that the effects of IL-17 mediate activation of STAT3 signaling in BC cells. Taken together, our study shows that MDSCs can be a new type prognostic marker in BC patient. Targeting IL-17/Stat3 signaling may be a promising strategy for BC treatment.
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