ArticleHepatology (Baltimore, Md.)2020
Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 1 of them a synthesis that pooled it.
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Who cites it
211 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical outcomes of immune checkpoint inhibitor combined with other targeted or immunological therapy regimens for the treatment of advanced bile tract cancer: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers: An open-label, non-randomized, phase II clinical trial.World journal of gastroenterology · 2024Trial
- Combining Selective Internal Radiation Therapy (SIRT) and Systemic Therapy in Intrahepatic Cholangiocarcinoma.Cancers · 2026Article
- Engineered Natural Killer Cell Derived-Extracellular Vesicles: An Acellular Immunotherapy with Cytotoxic Effects in SNU-1079 Human Cholangiocarcinoma Cells.Molecular pharmaceutics · 2026Article
- Mitochondria related gene signature serves as prognosis prediction and risk stratification of cholangiocarcinoma.Translational cancer research · 2026Article
- Review
- A Phase II Trial of Pembrolizumab plus Granulocyte-Macrophage Colony-Stimulating Factor in Advanced Biliary Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Spatial Immune Remodeling Across the Gallbladder Carcinogenesis Spectrum: A Multicenter Digital Pathology Study.World journal of oncology · 2026Article
- Advances in Immunotherapy for Intrahepatic Cholangiocarcinoma.International journal of molecular sciences · 2026Review
- Real-world treatment patterns and early outcomes in advanced intrahepatic cholangiocarcinoma: a descriptive case series.Cancer immunology, immunotherapy : CII · 2026Article
- Tumor site influences efficacy of MEKi and immunotherapy combinations in a preclinical model of cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Role of the stromal and immune microenvironment in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2026Review
- The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.Cancers · 2026Review
- The expression status and clinical value of TIM-3 in intrahepatic cholangiocarcinoma.BMC cancer · 2026Article
- Perioperative approaches for patients with biliary tract cancer.Nature reviews. Clinical oncology · 2026Review
- Targeting regulatory T cells in gastrointestinal cancers: current status and future perspectives.International journal of clinical oncology · 2026Review
- Knowledge mapping of ⁹⁰Y transarterial radioembolization combined with immunotherapy in hepatocellular carcinoma: a bibliometric analysis.Discover oncology · 2026Article
- A prospective study of tumor-stroma ratio in resected intrahepatic mass-forming cholangiocarcinoma: prognostic value and correlation with gadoxetic acid-enhanced MRI.European radiology · 2026Article
- Biomarker-guided immuno-angiogenic therapy in biliary tract cancer: insights from IMbrave151.Journal of gastrointestinal oncology · 2026Article
- MARCO promotes cholangiocarcinogenesis by inducing immunosuppression and its targeting reduces tumor growth.Signal transduction and targeted therapy · 2026Article
151 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors.
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Abstract
BACKGROUND AND
aimsIntrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of the desmoplastic tumor microenvironment (TME) of ICC has been stressed but was insufficiently taken into account in the search for classifications of ICC adapted to clinical trial design. We investigated the heterogeneous tumor stroma composition and built a TME-based classification of ICC tumors that detects potentially targetable ICC subtypes. APPROACH AND
resultsWe established the bulk gene expression profiles of 78 ICCs. Epithelial and stromal compartments of 23 ICCs were laser microdissected. We quantified 14 gene expression signatures of the TME and those of 3 functional indicators (liver activity, inflammation, immune resistance). The cell population abundances were quantified using the microenvironment cell population-counter package and compared with immunohistochemistry. We performed an unsupervised TME-based classification of 198 ICCs (training set) and 368 ICCs (validation set). We determined immune response and signaling features of the different immune subtypes by functional annotations. We showed that a set of 198 ICCs could be classified into 4 TME-based subtypes related to distinct immune escape mechanisms and patient outcomes. The validity of these immune subtypes was confirmed over an independent set of 368 ICCs and by immunohistochemical analysis of 64 ICC tissue samples. About 45% of ICCs displayed an immune desert phenotype. The other subtypes differed in nature (lymphoid, myeloid, mesenchymal) and abundance of tumor-infiltrating cells. The inflamed subtype (11%) presented a massive T lymphocyte infiltration, an activation of inflammatory and immune checkpoint pathways, and was associated with the longest patient survival.
conclusionWe showed the existence of an inflamed ICC subtype, which is potentially treatable with checkpoint blockade immunotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.