ArticleProceedings of the National Academy of Sciences of the United States of America2022
Epigenetic state determines inflammatory sensing in neuroblastoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 50 citations in OpenAlex.
- Telomere damage enhances immunogenicity of neuroblastoma and accelerates response to anti-PD-L1 treatment.Oncoimmunology · 2026Article
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Toll-like Receptor 3 as a Context-Dependent Molecular Switch in Epithelial Cancers: Balancing Cell Death and Tumor-Supportive Programs.International journal of molecular sciences · 2026Review
- Hypoxia Promotes an Adrenergic to Mesenchymal Transcriptional Program Transition in Neuroblastoma.Clinical and translational science · 2026Article
- Review
- Review
- Target antigen-displaying extracellular vesicles boost CAR T cell efficacy in cell and mouse models of neuroblastoma.Science translational medicine · 2025Article
- RBM39 degrader invigorates innate immunity to eradicate neuroblastoma despite cancer cell plasticity.Nature communications · 2025Article
- MYC: The Guardian of Its Own Chaos.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Lineage dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and -independent immunotherapeutic targets.Neuro-oncology · 2025Article
- The Interaction Between Vasculogenic Mimicry and the Immune System: Mechanistic Insights and Dual Exploration in Cancer Therapy.Cell proliferation · 2025Review
- Three-Dimensional Culture Systems in Neuroblastoma Research.Organoids · 2025Article
- A drug that induces the microRNA miR-124 enables differentiation of retinoic acid-resistant neuroblastoma cells.Science signaling · 2025Article
- The STING Signaling: A Novel Target for Central Nervous System Diseases.Cellular and molecular neurobiology · 2025Review
- Loss of ARID1A leads to a cold tumor phenotype via suppression of IFNγ signaling.Scientific reports · 2025Article
- T cells in the microenvironment of solid pediatric tumors: the case of neuroblastoma.Frontiers in immunology · 2025Review
- Identification and Characterization of Chemotherapy-Resistant High-Risk Neuroblastoma Persister Cells.Cancer discovery · 2024Article
- Cell state plasticity in neuroblastoma.EJC paediatric oncology · 2024Article
- Immune evasion: An imperative and consequence of MYC deregulation.Molecular oncology · 2024Review
- Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Immunotherapy has revolutionized cancer treatment, but many cancers are not impacted by currently available immunotherapeutic strategies. Here, we investigated inflammatory signaling pathways in neuroblastoma, a classically "cold" pediatric cancer. By testing the functional response of a panel of 20 diverse neuroblastoma cell lines to three different inflammatory stimuli, we found that all cell lines have intact interferon signaling, and all but one lack functional cytosolic DNA sensing via cGAS-STING. However, double-stranded RNA (dsRNA) sensing via Toll-like receptor 3 (TLR3) was heterogeneous, as was signaling through other dsRNA sensors and TLRs more broadly. Seven cell lines showed robust response to dsRNA, six of which are in the mesenchymal epigenetic state, while all unresponsive cell lines are in the adrenergic state. Genetically switching adrenergic cell lines toward the mesenchymal state fully restored responsiveness. In responsive cells, dsRNA sensing results in the secretion of proinflammatory cytokines, enrichment of inflammatory transcriptomic signatures, and increased tumor killing by T cells in vitro. Using single-cell RNA sequencing data, we show that human neuroblastoma cells with stronger mesenchymal signatures have a higher basal inflammatory state, demonstrating intratumoral heterogeneity in inflammatory signaling that has significant implications for immunotherapeutic strategies in this aggressive childhood cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.