Molecular and cellular consequences of tumour-autonomous IL-6 signalling in intrahepatic cholangiocarcinoma - PubMed
7 hours ago
- #IL-6 signaling
- #tumor microenvironment
- #cholangiocarcinoma
- High serum IL-6 levels predict poor prognosis in intrahepatic cholangiocarcinoma (iCCA).
- Tumor cells autonomously produce and engage autocrine IL-6 signaling, but its consequences were unknown.
- CRISPR-activated IL-6high iCCA cell models were generated and analyzed via RNA-sequencing and secretome analysis.
- Chronic IL-6 signaling drives distinct transcriptional programs, metabolic vulnerabilities, and immunomodulatory effects.
- IL-6high tumor cells show sensitivity to nicotinamide phosphoribosyltransferase inhibition, disrupting mitochondrial fitness.
- IL-6 signaling alters the tumor secretome, modulating immune cell composition and impairing macrophage efferocytosis.
- Spatial transcriptomics reveal tumor IL6 expression correlates with myeloid cell depletion and CAF enrichment.
- The study uncovers IL-6's role in shaping tumor-intrinsic and microenvironmental features, revealing therapeutic vulnerabilities.