Spatiotemporal analyses of the pan-cancer single-cell landscape reveal widespread profibrotic ecotypes associated with tumor immunity.

The tumor microenvironment evolves during tumor development and influences the cells in the microenvironment to orchestrate a supportive environment for tumor growth. Here we collected 4,483,367 cells across 36 cancer types and constructed a pan-cancer resource named TabulaTIME. Our integrated analyses reveal that CTHRC1 is a hallmark of extracellular matrix-related cancer-associated fibroblasts (CAFs) that are enriched in different cancer types. Spatiotemporal analyses further indicated that CTHRC1 CAFs are located at the leading edge between the malignant and normal regions, potentially preventing immune infiltration. Moreover, we identified that SLPI macrophages exhibit profibrotic-associated phenotypes and colocalize with CTHRC1 CAFs to form unique spatial ecotypes. Finally, we demonstrated that TabulaTIME can be used to analyze tumor ecotype composition and can serve as a reference for cell-type annotation. This work establishes a comprehensive single-cell landscape of the heterogenous TME and offers a potential therapeutic strategy for targeting the profibrotic ecotype in cancer treatment.