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<p>Liver metastasis is a frequent and clinically important event across multiple solid tumors, yet a cross-cancer single-cell description of the metastatic immune ecosystem remains incomplete. Here, we integrated single-cell RNA-sequencing data from primary tumors and liver metastases across 12 cancer types and combined cell-state annotation, pseudotime ordering, ligand–receptor inference, and multiplex immunofluorescence as orthogonal tissue-level support. We identified a hepatocyte-like malignant epithelial state enriched in liver metastases, characterized by coexpression of hepatic genes, epithelial markers, oncogenic transcripts such as MYC and KRAS, and inferred copy-number-variation signals. CellChat analysis suggested that this epithelial state may engage RGS1-high and LILRB5-high macrophage states through a CCL3–CCR1-associated signaling axis. Reprocessed tissue imaging supported spatial proximity between TAT+/EPCAM+ epithelial cells and these macrophage populations across several tumor types. In addition, macrophage and T-cell composition differed between primary tumors and liver metastases, and sample-level associations linked RGS1-high macrophages to selected CD4 + T-cell states and LILRB5-high resident-like macrophages to selected CD8 + T-cell states. Overall, this study provides a pancancer descriptive atlas of epithelial–immune programs associated with liver metastasis and nominates candidate cellular associations for future functional testing.</p>

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Single-cell pancancer analysis reveals epithelial–immune crosstalk in shaping the premetastatic niche of liver metastasis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月30日

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  • Hua-Kai Wang,
  • Qiu-Yi Tang,
  • Zi-You Wu,
  • Yue Yang,
  • Yi-Di Zhu,
  • Zi-Yi Yang,
  • Shi-Lei Liu,
  • Yu Zhang,
  • Wen-Ting Dai,
  • Yi-Jian Zhang,
  • Hong-Gang Xiang,
  • Ke-Zhou Wang,
  • Wei Gong

摘要

Liver metastasis is a frequent and clinically important event across multiple solid tumors, yet a cross-cancer single-cell description of the metastatic immune ecosystem remains incomplete. Here, we integrated single-cell RNA-sequencing data from primary tumors and liver metastases across 12 cancer types and combined cell-state annotation, pseudotime ordering, ligand–receptor inference, and multiplex immunofluorescence as orthogonal tissue-level support. We identified a hepatocyte-like malignant epithelial state enriched in liver metastases, characterized by coexpression of hepatic genes, epithelial markers, oncogenic transcripts such as MYC and KRAS, and inferred copy-number-variation signals. CellChat analysis suggested that this epithelial state may engage RGS1-high and LILRB5-high macrophage states through a CCL3–CCR1-associated signaling axis. Reprocessed tissue imaging supported spatial proximity between TAT+/EPCAM+ epithelial cells and these macrophage populations across several tumor types. In addition, macrophage and T-cell composition differed between primary tumors and liver metastases, and sample-level associations linked RGS1-high macrophages to selected CD4 + T-cell states and LILRB5-high resident-like macrophages to selected CD8 + T-cell states. Overall, this study provides a pancancer descriptive atlas of epithelial–immune programs associated with liver metastasis and nominates candidate cellular associations for future functional testing.