ArticleBMC medicine2025
Multi-omics analysis uncovers predictive biomarkers for the efficacy and outcomes of chemoimmunotherapy in advanced unresectable biliary tract cancers.
Article in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- First-Line Pembrolizumab Plus Chemotherapy for Advanced Biliary Tract Cancer: China Subgroup Analysis of the Randomized Phase 3 KEYNOTE-966 Study.Advances in therapy · 2026Trial
- Exploratory genomic stratification of benefit from first-line immunotherapy-based combination in advanced biliary tract cancer: a biomarker analysis of a randomized phase 2 trial.Frontiers in immunology · 2026Trial
- Targeting the cytokine-epigenetic axis: a new paradigm and prospects for disease treatment.European cytokine network · 2026Review
- Bevacizumab in biliary tract cancer: a clinical catalyst in the era of chemo-immunotherapy?Journal of gastrointestinal oncology · 2026Article
- Xiaoyao San alleviates emotional distress - induced TNBC growth through augmenting intratumoral CD8Frontiers in immunology · 2026Article
- Single-cell multi-omics in biliary tract cancers: decoding heterogeneity, microenvironment, and treatment strategies.Molecular biomedicine · 2025Review
- Review
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
backgroundThe limited response rates of immune checkpoint inhibitors in biliary tract cancers (BTC) highlight the need for effective biomarkers to optimize patient selection.
methodsBaseline tumor tissues from 125 patients with advanced BTC treated with first-line chemoimmunotherapy (chemoIO) were analyzed using targeted DNA sequencing and bulk RNA sequencing. In vitro and in vivo experiments were conducted to investigate the role of identified biomarkers in BTC.
resultsMutations in TP53, BRCA2, cytokine genes, and high tumor mutation burden were significantly associated with treatment response. In contrast, KRAS G12D and ARID1A mutations were linked to poorer survival outcomes. High expression levels of CXCL9 and CTLA4 expression were associated with improved treatment response, prolonged progression-free survival, and overall survival. Using these biomarkers, patients were categorized into three molecular subtypes, with Type I patients demonstrating the most favorable outcomes under chemoIO. Subsequent RNA analysis revealed that elevated CXCL9 expression was associated with increased immune checkpoint expression within the tumor and heightened immune activity in the tumor microenvironment. In the mouse orthotopic cholangiocarcinoma model, CXCL9 overexpression enhanced chemoIO efficacy. Immunohistochemistry and flow cytometry showed that CXCL9 promoted T-cell infiltration and activation. In vitro experiments using multiple BTC cell lines further demonstrated that CXCL9 was essential for maintaining T cell cytotoxicity. The immune-modulatory effects of CXCL9/CTLA4 and their predictive value for treatment efficacy were further validated in a multicenter BTC cohort.
conclusionsThis study identified several predictive biomarkers associated with the response and efficacy of chemoIO in advanced BTC, offering valuable insights into patient stratification and refining therapeutic strategies.
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