Tumor-neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression.
Proc Natl Acad Sci U S A
; 121(20): e2312855121, 2024 May 14.
Article
in En
| MEDLINE
| ID: mdl-38713626
ABSTRACT
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 CCL3highPD-L1high 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urinary Bladder Neoplasms
/
Interleukin-8
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Disease Progression
/
Tumor Microenvironment
/
Neutrophils
Limits:
Animals
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Female
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Humans
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Male
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2024
Type:
Article
Affiliation country:
China