膀胱癌
癌症研究
癌症
炎症
恶性肿瘤
信号转导
车站3
肿瘤微环境
促炎细胞因子
生物
免疫学
免疫系统
医学
病理
内科学
生物化学
作者
Jelena Korać-Prlić,Marina Degoricija,Katarina Vilović,Benedikt Haupt,Tonči Ivanišević,Lucija Franković,Sergei I. Grivennikov,Janoš Terzić
标识
DOI:10.1016/j.canlet.2020.06.018
摘要
Bladder cancer is the fourth most commonly diagnosed malignancy in men worldwide and has one of the highest recurrence rates of all cancers. This cancer type is unique because chronic inflammation caused by Schistosoma haematobium can cause bladder cancer, while inflammation induced by Bacillus Calmette Guerin is the therapeutic cornerstone for this cancer type. Activation of proinflammatory IL-6/Stat3 axis promotes the development of different cancers by acting on cancer cells as well as by modulating cancer microenvironment. Using a genetic and pharmacological approach in a mouse model, we demonstrated the importance of IL-6 and Stat3 signaling in bladder cancer. Our findings show that pharmacological inhibition of Stat3 with WP1066 effectively delays progression and invasiveness of bladder cancer in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced mouse model. Moreover, either IL-6 blockade or Stat3 inhibition sensitized bladder cancer to anti-PD-L1 immune therapy. Taken together, our study demonstrates an important role of IL-6/Stat3 signaling in bladder cancer and creates a rationale for testing the therapeutic potential of Stat3 inhibitors in human MIBC both alone or in combination with anti-PD-L1 and anti-IL-6 therapy.
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