Senescent-Like Neutrophils Shape Angiogenic Immunosuppressive Niches in Colorectal Cancer Liver Metastasis.
Senescent-like neutrophils expressing BHLHE40 promote immunosuppressive and angiogenic niches in colorectal cancer liver metastasis, correlating with poor prognosis.
- Why it matters: Understanding how neutrophils contribute to tumor progression in CRLM is crucial, as their roles in shaping the tumor microenvironment remain unclear, limiting targeted therapies.
- What they did: Using single-cell RNA sequencing and Stereo-seq, the study identified a pro-tumor neutrophil subset (TAN1) enriched in liver metastases, driven by glucose deprivation and BHLHE40 upregulation.
- The result: BHLHE40+ neutrophils facilitate angiogenesis and recruit immunosuppressive macrophages, and knocking out Bhlhe40 enhances anti-tumor immunity, highlighting potential therapeutic targets.