肿瘤微环境
癌症
癌症研究
肿瘤进展
膀胱癌
生物
免疫学
医学
肿瘤细胞
内科学
作者
Weiqiang Jing,Ganyu Wang,Zhiwei Cui,Xinyuan Li,Shuyan Zeng,Xin Jiang,Wushan Li,Bo Han,Nianzeng Xing,Yunxue Zhao,Xinguo Hou,Benkang Shi
标识
DOI:10.1073/pnas.2312855121
摘要
The immune landscape of bladder cancer progression is not fully understood, and effective therapies are lacking in advanced bladder cancer. Here, we visualized that bladder cancer cells recruited neutrophils by secreting interleukin-8 (IL-8); in turn, neutrophils played dual functions in bladder cancer, including hepatocyte growth factor (HGF) release and CCL3 high PD-L1 high super-immunosuppressive subset formation. Mechanistically, c-Fos was identified as the mediator of HGF up-regulating IL-8 transcription in bladder cancer cells, which was central to the positive feedback of neutrophil recruitment. Clinically, compared with serum IL-8, urine IL-8 was a better biomarker for bladder cancer prognosis and clinical benefit of immune checkpoint blockade (ICB). Additionally, targeting neutrophils or hepatocyte growth factor receptor (MET) signaling combined with ICB inhibited bladder cancer progression and boosted the antitumor effect of CD8 + T cells in mice. These findings reveal the mechanism by which tumor–neutrophil cross talk orchestrates the bladder cancer microenvironment and provide combination strategies, which may have broad impacts on patients suffering from malignancies enriched with neutrophils.
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