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Multi-omics profiling reveals cholic acid-mediated immunosuppression driven by peritumoral ductular reactions in hepatocellular carcinoma - PubMed

12 hours ago
  • #Cholic acid
  • #Immunosuppression
  • #Hepatocellular carcinoma
  • Multi-omics profiling reveals cholic acid-mediated immunosuppression in hepatocellular carcinoma (HCC).
  • Peritumoral ductular reactions predict poor clinical outcomes and correlate with cirrhosis severity.
  • Three distinct cholangiocyte subpopulations identified, with Small_duct_type_Cho promoting stromal remodeling.
  • Cholic acid enrichment at tumor margins induces CD8+ T cell dysfunction via NR1H4-dependent PD1 upregulation.
  • NR1H4 inhibition synergizes with anti-PD1 therapy, significantly suppressing tumor growth in murine models.
  • Ductular reactions serve as both a prognostic biomarker and therapeutic target in HCC.