泛癌肝转移的单细胞图谱揭示驱动转移进展和免疫调节的动态细胞程序

Liver metastasis remains a major challenge in cancer treatment, yet its cellular and molecular landscape remains poorly defined at the pan-cancer level.

Here, we construct a single-cell transcriptomic atlas of liver metastases across multiple cancer types by analyzing 100 single-cell RNA sequencing samples, profiling over 460,000 cells, and identifying 121 distinct cellular subtypes.

We define 4 representative cellular programs (CPs) associated with liver metastasis, revealing how cellular composition and intercellular interactions within the tumor microenvironment drive metastatic progression and immune modulation.

These CPs recapitulate a dynamic transition from immunoactive states, marked by natural-killer-cell-mediated immune surveillance and macrophage-driven angiogenesis, to immunosuppressive environments dominated by regulatory T cell infiltration and immune exclusion. The shift is marked by progressive alterations in immune infiltration, stromal remodeling, and tumor-intrinsic adaptations, elucidating key mechanisms of immune evasion and metastatic niche formation.

Our study provides a high-resolution framework for understanding the heterogeneity and evolution of liver metastasis and highlights the potential of CP-based stratification to inform therapeutic strategies targeting the metastatic tumor microenvironment.