Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring DOI Creative Commons
Wenbao Yu,

Rumeysa Biyik‐Sit,

Yasin Uzun

et al.

Nature Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract High-risk neuroblastoma, a leading cause of pediatric cancer mortality, exhibits substantial intratumoral heterogeneity, contributing to therapeutic resistance. To understand tumor microenvironment evolution during therapy, we longitudinally profiled 22 patients with high-risk neuroblastoma before and after induction chemotherapy using single-nucleus RNA ATAC sequencing whole-genome sequencing. This revealed profound shifts in immune cell subpopulations therapy identified enhancer-driven transcriptional regulators neoplastic states. Poor outcome correlated proliferative metabolically active states, whereas more differentiated neuronal-like states predicted better prognosis. Proportions mesenchymal cells increased high proportion poorer response. Macrophages significantly expanded towards pro-angiogenic, immunosuppressive metabolic phenotypes. We paracrine signaling networks validated the HB-EGF–ERBB4 axis between macrophage subsets, which promoted growth through ERK signaling. These findings collectively reveal intrinsic extrinsic response neuroblastoma.

Language: Английский

Longitudinal single-cell multiomic atlas of high-risk neuroblastoma reveals chemotherapy-induced tumor microenvironment rewiring DOI Creative Commons
Wenbao Yu,

Rumeysa Biyik‐Sit,

Yasin Uzun

et al.

Nature Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract High-risk neuroblastoma, a leading cause of pediatric cancer mortality, exhibits substantial intratumoral heterogeneity, contributing to therapeutic resistance. To understand tumor microenvironment evolution during therapy, we longitudinally profiled 22 patients with high-risk neuroblastoma before and after induction chemotherapy using single-nucleus RNA ATAC sequencing whole-genome sequencing. This revealed profound shifts in immune cell subpopulations therapy identified enhancer-driven transcriptional regulators neoplastic states. Poor outcome correlated proliferative metabolically active states, whereas more differentiated neuronal-like states predicted better prognosis. Proportions mesenchymal cells increased high proportion poorer response. Macrophages significantly expanded towards pro-angiogenic, immunosuppressive metabolic phenotypes. We paracrine signaling networks validated the HB-EGF–ERBB4 axis between macrophage subsets, which promoted growth through ERK signaling. These findings collectively reveal intrinsic extrinsic response neuroblastoma.

Language: Английский

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