Spatial mapping of state transitions at the tumor-stroma interface in bladder cancer

The tumor-stroma local interfaces (TSLIs) are functionally critical, dynamic regions that influence cancer progression, invasiveness, and anti-tumor immunity. Transcriptional programs and intercellular interactions suggest that some TSLIs are active - associated with epithelial-mesenchymal transition (EMT) and tissue remodeling - while others are predominantly passive or transient. Analyzing a cohort of bladder tumors with diverse histology, we identify key patterns of intercellular signaling, influencing EMT and cancer hallmarks associated with the transitions between active and passive segments in the heterogeneous TSLI regions. In bladder tumors, the functional state transitions across the TSLI are often gradual - occurring on a ~100 μm scale, modulated by MK, PDGF, and TGFB signaling involving tumor and non-tumor cell types in the local niche. Tumor subclones influence TSLI state transition patterns in their neighborhood. The prevalence, spatial distribution, and organization of TSLI states appear tumor-subtype dependent and may influence tumor evolutionary trajectories and invasive potential.