ArticleCell reports. Medicine2025
Molecular subtypes of hepatocellular carcinoma linked to liver cell lineages and clinical outcomes of combination immunotherapy.
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed.
- Unmasking Wnt-driven HCC: Inhibiting SMYD2 to overcome immune resistance.Molecular therapy. Oncology · 2026Article
- A mitochondrial function-based prognostic model for hepatocellular carcinoma uncovers MRPS15 as a key driver of tumor progression through oxidative phosphorylation.Translational cancer research · 2026Article
- From Theory to Practice: Which Biomarkers Are Ready for Predicting Response in Advanced HCC?Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Artificial intelligence driven exposome and multi omics integration for biomarker discovery in liver cancer: a literature review.Frontiers in immunology · 2026Review
- Diagnosis, clinical assessment, and staging of hepatocellular carcinoma: a Brazilian multidisciplinary consensus.Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery · 2026Article
Corrections and comments
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Authors and funding
23 authors.
Funding
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Abstract
Understanding the biology and clinical relevance of disease heterogeneity in hepatocellular carcinoma (HCC) is important for guiding therapeutic strategies. Through multi-omics and in situ analyses in three independent cohorts of patients with advanced HCC including GO30140 phase 1b and IMbrave150 phase 3 trials, we identified three robust molecular subtypes of HCC, i.e., cholangiocyte-like, progenitor-like, and hepatocyte-like, based on their association with different liver epithelial cell lineages. These subtypes showed distinct tumor cell-intrinsic and extrinsic features, including different immune contextures, and importantly an association with clinical response to atezolizumab plus bevacizumab combination immunotherapy. In a humanized HCC xenograft mouse model recapitulating the GPC3-high progenitor-like subtype, a GPC3/CD3 bispecific antibody elicited strong antitumor activity mediated by intratumoral recruitment and activation of T cells. Our study provides biological insights into HCC heterogeneity and potential strategies for targeting subtype-specific vulnerabilities.
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Registered trials
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