Senescent-Like Neutrophils Shape Angiogenic Immunosuppressive Niches in Colorectal Cancer Liver Metastasis.

A senescent-like neutrophil subset marked by BHLHE40 is enriched in colorectal cancer liver metastasis and linked to poor prognosis.

• Why it matters: Understanding neutrophil roles in CRLM is crucial because their functions in shaping the tumor microenvironment are not well characterized, limiting potential therapeutic strategies.
• What they did: Using single-cell RNA sequencing and Stereo-seq, the study identified a terminally differentiated pro-tumor neutrophil subset (TAN1) with a glycolysis signature and senescent phenotype, which arises via BHLHE40 upregulation driven by glucose deprivation.
• The result: BHLHE40+ neutrophils promote angiogenesis and immunosuppression, and neutrophil-specific Bhlhe40 knockout in mice enhances anti-tumor immunity, suggesting targeting this pathway could improve CRLM treatment.