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Single-cell profiles delineate immune cell remodeling and enhanced tumor-fibroblast interaction of hepatoblastoma after chemotherapy

ABSTRACT: Hepatoblastoma (HB), the most common pediatric liver cancer, is typically treated with chemotherapy, yet its impact on the tumor microenvironment (TME) and mechanisms of chemoresistance remain unclear. We perform single-cell RNA sequencing on 32 HB tumors pre- and post-chemotherapy, integrating data from spatial transcriptomics, bulk transcriptomics, multiplexed immunofluorescence, and patient-derived xenografts. Chemotherapy enriches CD69⁺CD8⁺ T cells and shifted myeloid cells toward immune-activating phenotypes. HB tumor cells exhibit both hepatic and mesenchymal features, with hepatic-like cells showing greater chemoresistance. A subset of AFP-high hepatic tumor cells expresses high FGFR4 and showed elevated proliferation. Post-treatment, mesenchymal-like tumor cells and MMP11⁺ cancer-associated fibroblasts enhance FGF-FGFR signaling. FGFR4 inhibition significantly suppressed tumor growth in xenografts. These findings provide a high-resolution landscape of the HB immune TME and highlight cancer–fibroblast interactions, especially via FGF signaling, as key contributors to chemoresistance.

ORGANISM(S): Homo sapiens

PROVIDER: GSE326150 | GEO | 2026/03/27

REPOSITORIES: GEO

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