骨髓
签名(拓扑)
癌症研究
神经母细胞瘤
医学
病理
骨重建
生物
内科学
细胞培养
几何学
数学
遗传学
作者
Shenglin Mei,Adele M. Alchahin,Bethel Tesfai Embaie,Ioana Maria Gavriliuc,Bronte Manouk Verhoeven,Ting Zhao,Xiangyun Li,Nathan Elias Jeffries,Adena Pepich,Hirak Sarkar,Thale Kristin Olsen,Malin Wickström,Jakob Stenman,Oscar Reina-Bedoya,Peter V. Kharchenko,Philip J. Saylor,John Inge Johnsen,David B. Sykes,Per Kogner,Ninib Baryawno
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2024-02-15
标识
DOI:10.1172/jci.insight.173337
摘要
Neuroblastoma is an aggressive pediatric cancer with a high rate of metastasis to the bone marrow. Despite intensive treatments including high-dose chemotherapy, the overall survival rate for children with metastatic neuroblastoma remains dismal. Understanding the cellular and molecular mechanisms of the metastatic tumor microenvironment is crucial for developing new therapies and improving clinical outcomes. Here, we used single-cell RNA-sequencing to characterize immune and tumor cell alterations in neuroblastoma bone marrow metastases by comparative analysis with patients without metastases. Our results revealed remodeling of the immune cell populations and reprogramming of gene expression profiles in the metastatic niche. In particular, within the bone marrow metastatic niche we observed the enrichment of immune cells, including tumor-associated neutrophils, macrophages, and exhausted T cells, as well as an increased number of regulatory T cells and a decreased number of B cells. Furthermore, we highlighted cell communication between tumor cells and immune cell populations, and identified prognostic markers in malignant cells that are associated with worse clinical outcomes in three independent neuroblastoma cohorts. Our results provide insights into the cellular, compositional and transcriptional shifts underlying neuroblastoma bone marrow metastases contributing to the development of new therapeutic strategies.
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