Evidence map›Paper›PMID 42900155›Full record

ArticleHepatology communications2026

Genomic and immune profiling characterizes immune heterogeneity and a TIGIT-associated subtype in intrahepatic cholangiocarcinoma.

Anastasiia Korosteleva, Josephine Sophie Reschke, Dawei Yi, Silke Marhenke, Jinbo Zhao, Valery Volk, Tanja Reineke-Plaaß, Simon Peter, Charlotte Hoffmann, Doan Duy Hai Tran and 7 more

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Article in Hepatology communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Anastasiia KorostelevaSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.ORCID 0000-0002-2016-4788
Josephine Sophie ReschkeDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Dawei YiDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Silke MarhenkeDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID 0000-0001-9053-293
Jinbo ZhaoSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Valery VolkInstitute of Pathology, Hannover Medical School, Hannover, Germany.
Tanja Reineke-PlaaßInstitute of Pathology, Hannover Medical School, Hannover, Germany.
Simon PeterDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Charlotte HoffmannDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Doan Duy Hai TranDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.
Christoph GerdesDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID 0000-0001-5351-5348
Melanie BathonDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID 0009-0002-1308-4656
Walter KolchSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Friedrich FeuerhakeInstitute of Pathology, Hannover Medical School, Hannover, Germany.ORCID 0000-0002-1234-982
Vadim ZhernovkovSystems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Anna SaborowskiDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID 0000-0003-4857-4276
Arndt VogelDept. of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hannover, Germany.ORCID 0000-0003-0560-5538

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntrahepatic cholangiocarcinoma (iCCA) is characterized by marked molecular and microenvironmental heterogeneity and moderate response to immunotherapy. We aimed to define the genomic and spatial determinants of immune checkpoint activity in iCCA and their association with clinical outcome.

methodsWe performed integrated transcriptomic, DNA panel sequencing, and multiplex immunohistochemistry analyses in a cohort of 144 patients with iCCA. Tumors were classified according to STIM-defined microenvironmental subtypes. Spatially resolved immune profiling was conducted across the tumor core, stroma, invasive margin, and adjacent liver. Immune checkpoint expression, cellular proximity, and clinical outcome were analyzed using Cox regression and Kaplan-Meier methods. TIGIThigh tumors were further characterized by differential gene expression and pathway enrichment analyses.ResultsSTIM classification stratified tumors into inflamed (47%) and non-inflamed (53%) subtypes with distinct survival outcomes and genomic profiles. Recurrent alterations in CDKN2A/B, TP53, MTAP, and BAP1 showed subtype-specific enrichment and prognostic relevance. Spatial immune profiling revealed compartment-specific distributions of T cells and immune checkpoints, with predominance of TIGIT and PD-1 expression in stromal and marginal regions. Most tumor-infiltrating T cells lacked inhibitory receptor expression, while co-expression of multiple checkpoints was uncommon. TIGIThigh tumors displayed coordinated activation of immune effector, antigen presentation, and interferon signaling pathways, alongside enrichment of distinct genomic alterations, defining an immune-activated molecular subtype.

conclusionIntegrated genomic and spatial immune profiling reveals pronounced context-dependent heterogeneity of immune checkpoint regulation in iCCA. TIGIT delineates an immune-activated subtype with distinct molecular features, providing a potential biomarker framework for patient stratification and rational immunotherapeutic targeting.

Indexed as

Bile Duct NeoplasmsCholangiocarcinomaReceptors, ImmunologicAgedBiomarkers, TumorFemaleGene Expression ProfilingGenomicsHumansMaleMiddle AgedPrognosisTumor MicroenvironmentBiomarkers, TumorReceptors, ImmunologicTIGIT protein, humanbiliary tract cancergenomic alterationsimmunotherapyprecision medicinetargeted therapy

Identifiers

PMID42900155
PMCPMC13682834

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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.