Interleukin-1beta triggers the expansion of circulating granulocytic myeloid-derived suppressor cell subset dependent...

Chronic inflammation contributes to cancer development and progression. Although interleukin-1beta (IL-1β) has been observed to be associated with an general immune suppression of T cell response and the immunosuppression strongly correlates with accumulation of myeloid-derived suppressor cells (MDSCs), the relationship and mechanism between MDSCs expansion and IL-1β expression remain ambiguous. Here, we showed that the concentration of IL-1β was highly correlated with G-MDSC subset, rather than mo-MDSC subset. Recombinant IL-1β increased the percentage of G-MDSCs in the blood of tumor-bearing mice, and IL-1Ra attenuated the accumulation of G-MDSCs in the tumor-bearing mice. In addition, the IL-1β-overexpressing B16F10 cells induced higher level of G-MDSCs compared with wild-type B16F10 cells. Moreover, we found that the accumulation of G-MDSCs induced by IL-1β was dependent on the activation of extracellular signal-regulated kinases 1 and 2 (Erk1/2). Collectively, these findings show a novel role of IL-1β in G-MDSCs accumulation by activating Erk1/2, which suggests that IL-1β elimination or Erk1/2 signaling blockade could decrease G-MDSCs generation and thereby improve host immunosurveillance.