2. Academic Validation
  3. Single-cell profiles delineate immune cell remodeling and enhanced tumor-fibroblast interaction of hepatoblastoma after chemotherapy

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

  • Cell Rep Med. 2025 Oct 21;6(10):102401. doi: 10.1016/j.xcrm.2025.102401.
Deqian Chen 1,  Yong Zhan 1,  Enqing Zhou 1,  Huifen Chen 1,  Shuyang Dai 1,  Ran Yang 1,  Chunjing Ye 1,  Junfeng Wang 1,  Yi Li 1,  Yifei Lu 1,  Ying Fang 1,  Lian Chen 2,  Wei Yao 1,  Kai Li 1,  Shan Zheng 1,  Kuiran Dong 3,  Jia Wang 4,  Rui Dong 5
Affiliations

Affiliations

  • 1 Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China; Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China.
  • 2 Department of Pathology, Children's Hospital of Fudan University, Shanghai 201102, China.
  • 3 Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China; Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: kuirand@hotmail.com.
  • 4 Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China; Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: wj860520@163.com.
  • 5 Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai 201102, China; Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: rdong@fudan.edu.cn.
PMID: 41038160 DOI: 10.1016/j.xcrm.2025.102401
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 (scRNA-seq) 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 Fibroblast Growth Factor receptor 4 (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.

Keywords

cancer-associated fibroblasts; chemotherapy resistance; hepatoblastoma; single-cell RNA sequencing; tumor microenvironment.

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