IL‐6 Promotes the Proliferation and Immunosuppressive Function of Myeloid‐Derived Suppressor Cells via the MAPK Signaling Pathway in Bladder Cancer
Zhong Zheng, Xinyi Zheng, Yiwen Zhu, Zhixian Yao, Weiguang Zhao, Youjia Zhu, Feng Sun, Xingyu Mu, Yong Wang, Wanqing He, Zhihong Liu, Ke Wu, Junhua Zheng
Abstract
Muscle‐invasive bladder cancer (MIBC) is characterized by a highly complex immune environment, which is not well understood. Interleukin‐6 (IL‐6) is generated and secreted by multifarious types of cells, including tumor cells. This study was aimed at demonstrating that the levels of IL‐6 and the number of myeloid‐derived suppressor cells (MDSCs), with a positive correlation between them, increased in MIBC tissues, promoting MIBC cell proliferation, especially in patients with recurrence. In coculture analysis, MDSCs, with the stimulation of IL‐6, could significantly lower the proliferation ability of CD4 + or CD8 + T lymphocytes. Further, this study demonstrated that IL‐6 could upregulate the mitogen‐activated protein kinase (MAPK) signaling pathway in MDSCs. The MAPK signaling inhibitor, aloesin, partially reversed the effects of IL‐6 on MDSCs. These data suggested that IL‐6 promoted MIBC progression by not only accelerating proliferation but also improving the immune suppression ability of MDSCs through activating the MAPK signaling pathway.