Researchers utilized a comprehensive multimodal approach combining single-cell sequencing, spatial transcriptomics, and spatial proteomics across 54 neuroblastoma tumors and orthotopic patient-derived xenografts to resolve long-standing debates regarding cellular heterogeneity. By developing new adrenergic (ADRN) and mesenchymal (MES) gene signatures derived from early-passage xenografts rather than outdated cell lines, the study successfully identified malignant MES tumor cells and mapped their spatial segregation from the tumor microenvironment. Furthermore, the spatial and multi-omic analyses revealed that tumors exhibit distinct cellular neighborhoods where malignant populations remain isolated from immune cells. Finally, clinical survival analyses demonstrated that a higher composite MES-ADRN score is independently associated with inferior event-free and overall survival, offering a clinically relevant framework for risk stratification.
References:
Patel A G, Ashenberg O, Collins N B, et al. Spatial omics resolves adrenergic and mesenchymal cell states in neuroblastoma[J]. Cancer Cell, 2026.
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