ArticleJournal of biomedical science2024
Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis.
Article in Journal of biomedical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Review
- From Gut Microbiota to Hepatic Pre-Metastatic Niches: Mechanism and Translational Prospects of the Gut-Liver Axis in Regulating Colorectal Cancer Liver Metastasis.Microorganisms · 2026Review
- The Role of Neutrophils in Non-Alcoholic Fatty Liver Disease: Mechanisms and Clinical Significance.Journal of inflammation research · 2026Review
- Pleiotropic immunoregulation by bile acids in pathophysiology.Frontiers in immunology · 2026Review
- Machine learning-based hepatocellular carcinoma risk prediction model for patients with HBV-related compensated advanced chronic liver disease.Journal of cancer research and clinical oncology · 2025Article
- Emerging role of bile acids in colorectal liver metastasis: From molecular mechanism to clinical significance (Review).International journal of oncology · 2025Review
- Review
- Identification of galangin as a therapeutic candidate for primary biliary cholangitis via systematic druggable genome-wide Mendelian randomization analysis and experimental validation.Frontiers in pharmacology · 2025Article
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Authors and funding
10 authors.
Funding
Abstract
backgroundCholestasis is a common yet severe complication that occurs during the advancement of liver metastasis. However, how cholestasis impacts the development, treatment, and tumor microenvironment (TME) of liver metastasis remains to be elucidated.
methodsExtrahepatic and intrahepatic cholestatic mouse models with liver metastasis were established to detect the differential expression levels of genes, infiltration of immune cells and change in bile acid-associated metabolites by using RNA-Sequencing, flowcytometry, and liquid chromatography and mass spectrometry. Western blot was applied to neutrophils under the stimulation of primary bile acids (BAs) in vitro to study the mechanism of phenotypic alteration. In vitro coculture of BA-treated neutrophils with CD8
resultsCompared to non-cholestatic mice, the progression of liver metastasis of cholestatic mice was significantly accelerated, which was associated with increased neutrophil infiltration and T-cell exclusion. Both neutrophils and T cells expressed higher immunosuppressive markers in the cholestatic mouse model, further indicating that an immunosuppressive tumor microenvironment was induced during cholestasis. Although neutrophils deletion via anti-Ly6G antibody partially hindered liver metastasis progression, it reduced the overall survival of mice. Tauro-β-muricholic acid (Tβ-MCA) and Glycocholic acid (GCA), the two most abundant cholestasis-associated primary BAs, remarkably promoted the expression of Arg1 and iNOS on neutrophils via p38 MAPK signaling pathway. In addition, BAs-pretreated neutrophils significantly suppressed the activation and cytotoxic effects of CD8
conclusionsOur study reveals the TME of cholestasis-associated liver metastasis and proposes a new strategy for such patients by targeting bile acid anabolism.
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