This paper details a spatial transcriptomic analysis of metastatic pancreatic cancer across primary tumors and various metastatic sites (liver, lung, and peritoneum) from 13 rapid-autopsy patients. The research focuses on mapping the transcriptomic heterogeneity of cancer cells, clonal evolution, and the tumor microenvironment (TME) with high resolution. Key findings include discernible shifts in cancer-cell lineage states as the tumor metastasizes to different organs, particularly noting a pronounced difference between liver (basal-like predominant) and lung (classical predominant) metastases. The study also explores diverse, patient-specific clonal evolutionary trajectories and highlights the spatial co-localization of aggressive basal-like cancer cells with myofibroblastic cancer-associated fibroblasts (myCAFs), which mediate immune exclusion of plasma cells via the TGFB1/CXCL12–CXCR4 axis. Overall, the work underscores the significant transcriptomic and microenvironmental complexity of advanced pancreatic cancer, offering an invaluable resource for therapeutic discovery.

References:

• Pei G, Min J, Rajapakshe K I, et al. Spatial mapping of transcriptomic plasticity in metastatic pancreatic cancer[J]. Nature, 2025: 1-10.