Identification of Four Immune Subtypes Characterized by Distinct Composition and Functions of Tumor Microenvironment in Intrahepatic Cholangiocarcinoma

Hepatology, Journal Year: 2019, Volume and Issue: 72(3), P. 965 - 981

Published: Dec. 26, 2019

Intrahepatic cholangiocarcinoma (ICC) is a severe malignant tumor in which the standard therapies are mostly ineffective. The biological significance of desmoplastic microenvironment (TME) ICC has been stressed but was insufficiently taken into account search for classifications adapted to clinical trial design. We investigated heterogeneous stroma composition and built TME-based classification tumors that detects potentially targetable subtypes.We established bulk gene expression profiles 78 ICCs. Epithelial stromal compartments 23 ICCs were laser microdissected. quantified 14 signatures TME those 3 functional indicators (liver activity, inflammation, immune resistance). cell population abundances using population-counter package compared with immunohistochemistry. performed an unsupervised 198 (training set) 368 (validation set). determined response signaling features different subtypes by annotations. showed set could be classified 4 related distinct escape mechanisms patient outcomes. validity these confirmed over independent immunohistochemical analysis 64 tissue samples. About 45% displayed desert phenotype. other differed nature (lymphoid, myeloid, mesenchymal) abundance tumor-infiltrating cells. inflamed subtype (11%) presented massive T lymphocyte infiltration, activation inflammatory checkpoint pathways, associated longest survival.We existence subtype, treatable blockade immunotherapy.

Language: Английский

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Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma

Cancer Cell, Journal Year: 2021, Volume and Issue: 40(1), P. 70 - 87.e15

Published: Dec. 30, 2021

Language: Английский

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Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 76(5), P. 1109 - 1121

Published: Feb. 12, 2022

Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, whose incidence related mortality increasing. This study investigates the clinical course of CCA subtypes (intrahepatic [iCCA], perihilar [pCCA], distal [dCCA]) in pan-European cohort.The ENSCCA Registry multicenter observational study. Patients were included if they had histologically proven diagnosis between 2010-2019. Demographic, histomorphological, biochemical, studies performed.Overall, 2,234 patients enrolled (male/female=1.29). iCCA (n = 1,243) was associated with overweight/obesity chronic liver diseases involving cirrhosis and/or viral hepatitis; pCCA 592) primary sclerosing cholangitis; dCCA 399) choledocholithiasis. At diagnosis, 42.2% local disease, 29.4% locally advanced disease (LAD), 28.4% metastatic (MD). Serum CEA CA19-9 showed low diagnostic sensitivity, but their concomitant elevation increased risk presenting LAD (odds ratio 2.16; 95% CI 1.43-3.27) or MD 5.88; 3.69-9.25). undergoing resection (50.3%) best outcomes, particularly negative-resection margin (R0) (median overall survival [mOS] 45.1 months); however, involvement (R1) (hazard 1.92; 1.53-2.41; mOS 24.7 months) lymph node invasion 2.13; 1.55-2.94; 23.3 compromised prognosis. Among unresectable (49.6%), 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%), 4.0 supportive care (20.6%). iCCAs worse outcomes than p/dCCAs. ECOG performance status, independent prognostic factors.CCA frequently diagnosed at an stage, proportion fail to receive cancer-specific prognosis remains dismal. Identification preventable factors implementation surveillance high-risk populations are required decrease cancer-related mortality.This is, date, largest international (pan-European: 26 hospitals 11 countries) study, which cholangiocarcinoma has been investigated, comparing 3 based on latest International Classification Diseases 11th Edition (ICD-11) (i.e., intrahepatic [2C12], [2C18], [2C15] affected bile ducts), come into effect 2022. General tumor-type specific features factors, biomarker accuracy, as well patient management presented compared, outlining current state Europe.

Language: Английский

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Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma

Journal of Hepatology, Journal Year: 2020, Volume and Issue: 73(2), P. 315 - 327

Published: March 12, 2020

Language: Английский

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N7-Methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression

Molecular Cell, Journal Year: 2021, Volume and Issue: 81(16), P. 3339 - 3355.e8

Published: Aug. 1, 2021

Language: Английский

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