ArticleNature cancer2022
Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 101 citations in OpenAlex.
- Umbilical cord blood natural killer cells improve anti-GD2 antibody efficacy in neuroblastoma: from mouse to human.Oncoimmunology · 2026Article
- Dinutuximab beta with TEMIRI chemotherapy in relapsed/refractory neuroblastoma: Real-world insights into the open question of GD2 expression.Translational oncology · 2026Article
- Review
- Quantitative and sensitive neuroblastoma minimal residual disease detection using extrachromosomal DNA (ecDNA) breakpoints.bioRxiv : the preprint server for biology · 2026Article
- 5-hydroxymethylcytosine deposition mediates Polycomb repressive complex 2 function iniScience · 2026Article
- Model-dependent GD2 upregulation in Ewing sarcoma with the EZH2 inhibitor tazemetostat: Prerequisites for combination with GD2-specific CAR T cells.Research square · 2026Article
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- Single-cell and spatial omics reveals region-specific plasticity and therapeutic vulnerabilities in metastatic high-risk neuroblastoma.Science advances · 2026Article
- Inhibition of USP7 Destabilizes the Noncanonical PRC1.1 Complex and Induces Neuroblastoma Differentiation.Molecular cancer research : MCR · 2026Article
- Targeting GD2 with CAR-T Cell Therapy in Neuroblastoma: Updates, Challenges, and Future Perspectives.Current oncology reports · 2026Review
- Unveiling the molecular landscape: Long non-coding RNAs in neuroblastoma (Review).Oncology reports · 2026Review
- Efficacy and Tolerability of Topotecan/Cyclophosphamide/Dinutuximab in Relapsed and Refractory High-Risk Neuroblastoma: A Multi-Institutional Retrospective Study.Pediatric blood & cancer · 2026Article
- Defining the Functional Role and Potential as an Immunotherapeutic Target of ALCAM in Neuroblastoma.Molecular cancer therapeutics · 2026Article
- IL-18 metabolically reprograms CAR-expressing natural killer T cells and enhances their antitumor activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- Hypoxia Promotes an Adrenergic to Mesenchymal Transcriptional Program Transition in Neuroblastoma.Clinical and translational science · 2026Article
- Review
- Review
- HLA-Shuttle: A system for enhancing antigen presentation in immunologically cold tumors.Science advances · 2026Article
- Management of persistent soft tissue residuals exhibiting an imaging paradox (^123I-MIBG-negative/^68Ga-DOTA-NOC-positive) in high-risk neuroblastoma following immunotherapy: a case report.Frontiers in immunology · 2026Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 8 institutions in 1 country.
Funding
Abstract
Immunotherapy with anti-GD2 antibodies has advanced the treatment of children with high-risk neuroblastoma, but nearly half of patients relapse, and little is known about mechanisms of resistance to anti-GD2 therapy. Here, we show that reduced GD2 expression was significantly correlated with the mesenchymal cell state in neuroblastoma and that a forced adrenergic-to-mesenchymal transition (AMT) conferred downregulation of GD2 and resistance to anti-GD2 antibody. Mechanistically, low-GD2-expressing cell lines demonstrated significantly reduced expression of the ganglioside synthesis enzyme ST8SIA1 (GD3 synthase), resulting in a bottlenecking of GD2 synthesis. Pharmacologic inhibition of EZH2 resulted in epigenetic rewiring of mesenchymal neuroblastoma cells and re-expression of ST8SIA1, restoring surface expression of GD2 and sensitivity to anti-GD2 antibody. These data identify developmental lineage as a key determinant of sensitivity to anti-GD2 based immunotherapies and credential EZH2 inhibitors for clinical testing in combination with anti-GD2 antibody to enhance outcomes for children with neuroblastoma.
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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.