Study Maps Treatment-Resistant Neuroblastoma Cells Linked to Poor Prognosis
St. Jude researchers and collaborators assembled a large neuroblastoma cell dataset using single-cell RNA sequencing and spatial omics to define tumor cell types. They identified a gene expression signature for malignant mesenchymal cells associated with high-risk disease, treatment resistance, and poor outcomes. Patient-derived xenograft models captured this population, offering new tools to study high-risk neuroblastoma.
Neuroblastoma, a childhood solid tumor arising outside the brain, has long puzzled clinicians because treatment responses vary widely. The study examined 54 tumors from 50 patients, combining single-cell RNA sequencing with spatial omics to catalog cell states. Adrenergic cells tend to accompany lower-risk disease, while mesenchymal cells are linked to aggressive, treatment-resistant tumors. Healthy mesenchymal cells complicate identification, so patient-derived xenografts helped isolate malignant mesenchymal cells and define their expression profile.
A new signature outperformed an older one derived from long-established cell lines when tested against independent patient RNA data. Researchers also generated organoids and cell lines, using spatial transcriptomics, spatial proteomics, electron microscopy, and chromatin profiling. These models and tools give researchers a way to study high-risk neuroblastoma.
Children with high-risk neuroblastoma and their families may benefit if this signature improves risk stratification or guides research into treatment resistance. Researchers could use the models to test hypotheses and develop therapies, though clinical benefit remains uncertain and likely years away. The work may also help distinguish malignant from healthy mesenchymal cells, reducing a barrier in pediatric cancer studies.