{"entity": "publication", "iuid": "d07b869d108e479b83a9f4334d611e25", "timestamp": "2026-04-12T03:53:49.028Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d07b869d108e479b83a9f4334d611e25.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d07b869d108e479b83a9f4334d611e25"}}, "title": "Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma.", "authors": [{"family": "Nagarajan", "given": "Divya", "initials": "D"}, {"family": "Parracho", "given": "Rebeca T", "initials": "RT"}, {"family": "Corujo", "given": "David", "initials": "D"}, {"family": "Xie", "given": "Minglu", "initials": "M"}, {"family": "Kutkaite", "given": "Ginte", "initials": "G", "orcid": "0000-0002-2918-294X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be0f080def0942e782116dca3d89c148.json"}}, {"family": "Olsen", "given": "Thale K", "initials": "TK"}, {"family": "R\u00fabies Bed\u00f3s", "given": "Marta", "initials": "M", "orcid": "0000-0003-0949-4329", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c25fafe4ed644a1890f9981b85c54e3d.json"}}, {"family": "Salehi", "given": "Maede", "initials": "M"}, {"family": "Baryawno", "given": "Ninib", "initials": "N"}, {"family": "Menden", "given": "Michael P", "initials": "MP", "orcid": "0000-0003-0267-5792", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/907d386ca4114274babf4703c976ecbe.json"}}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-3214-9075", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4a7d95a9799a4c23bb01bf05fa6351cc.json"}}, {"family": "Buschbeck", "given": "Marcus", "initials": "M"}, {"family": "Mao", "given": "Yumeng", "initials": "Y", "orcid": "0000-0001-6142-6628", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed7a1f5fdd354dad848c5f856d21d152.json"}}], "type": "journal article", "published": "2024-09-10", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "issn-l": "0021-9738"}, "abstract": "Childhood neuroblastoma with MYCN-amplification is classified as high-risk and often relapses after intensive treatments. Immune checkpoint blockade therapy against the PD-1/L1 axis shows limited efficacy in neuroblastoma patients and the cancer intrinsic immune regulatory network is poorly understood. Here, we leverage genome-wide CRISPR/Cas9 screens and identify H2AFY as a resistance gene to the clinically approved PD-1 blocking antibody, nivolumab. Analysis of single-cell RNA sequencing datasets reveals that H2AFY mRNA is enriched in adrenergic cancer cells and is associated with worse patient survival. Genetic deletion of H2afy in MYCN-driven neuroblastoma cells reverts in vivo resistance to PD-1 blockade by eliciting activation of the adaptive and innate immunity. Mapping of the epigenetic and translational landscape demonstrates that H2afy deletion promotes cell transition to a mesenchymal-like state. With a multi-omics approach, we uncover H2AFY-associated genes that are functionally relevant and prognostic in patients. Altogether, our study elucidates the role of H2AFY as an epigenetic gatekeeper for cell states and immunogenicity in high-risk neuroblastoma.", "doi": "10.1172/JCI175310", "pmid": "39255035", "labels": {"Yumeng Mao": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pii", "key": "175310"}], "notes": [], "created": "2024-10-29T15:43:38.571Z", "modified": "2025-04-07T06:59:54.593Z"}