Molecular subtypes of hepatocellular carcinoma linked to liver cell lineages and clinical outcomes of combination immunotherapy.

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 GPC

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12765846 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature