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However, systemic immune remodeling and its effect on the bone marrow niche remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Harnessing single-cell RNA sequencing, we compare the bone marrow immune cell landscape of wild-type (WT) mice and TH-\n                      <jats:italic>MYCN<\/jats:italic>\n                      transgenic mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TH-\n                      <jats:italic>MYCN<\/jats:italic>\n                      mice showed increased neutrophils and\n                      <jats:italic>Cd300e<\/jats:italic>\n                      + myeloid cells, and reduced developing B cells, mirroring our findings in human neuroblastoma bone marrow metastases. Ligand-receptor analysis revealed enrichment of ADGRG and SEMA4 signaling pathways in TH-\n                      <jats:italic>MYCN<\/jats:italic>\n                      bone marrow, highlighting Tgm2-Adgrg1, Sema4D-Plxnb2, and Sema4D-Cd72 interactions as potential immune modulators. In contrast, CD45 and CEACAM pathways were prominent in WT mice, suggesting context-specific immune regulation. A distinct\n                      <jats:italic>Cd300e<\/jats:italic>\n                      +\n                      <jats:italic>Pecam1<\/jats:italic>\n                      + myeloid population enriched in TH-\n                      <jats:italic>MYCN<\/jats:italic>\n                      mice, exhibited a gene signature, including\n                      <jats:italic>Fabp4<\/jats:italic>\n                      ,\n                      <jats:italic>Ear2<\/jats:italic>\n                      (\n                      <jats:italic>Nr2f6<\/jats:italic>\n                      ), and\n                      <jats:italic>Treml4<\/jats:italic>\n                      , genes associated with neuroblastoma staging and poor survival.\n                      <jats:italic>FABP4<\/jats:italic>\n                      + macrophages, enriched in\n                      <jats:italic>MYCN<\/jats:italic>\n                      -amplified neuroblastoma relapse, have been implicated in enhancing tumor cell migration, invasion, and growth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data reveals the distant influence of primary tumors on bone marrow immune composition and signaling. These insights into bone marrow immune remodeling highlight FABP4+ macrophages and semaphorin signaling as potential immunotherapeutic targets to disrupt neuroblastoma progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s44276-026-00249-3","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:48:15Z","timestamp":1789451295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune remodeling and myeloid signature in the bone marrow niche of MYCN-driven neuroblastoma"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7081-5032","authenticated-orcid":false,"given":"Bethel Tesfai","family":"Embaie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele M.","family":"Alchahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"Velentza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thale Kristin","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana Maria","family":"Gavriliuc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenglin","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninib","family":"Baryawno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"249_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/S12957-023-03011-Y","volume":"21","author":"S Liu","year":"2023","unstructured":"Liu S, Yin W, Lin Y, Huang S, Xue S, Sun G, et al. 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Front Pharmacol. 2022;13:948610. https:\/\/doi.org\/10.3389\/FPHAR.2022.948610.","journal-title":"Front Pharmacol"}],"container-title":["BJC Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44276-026-00249-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44276-026-00249-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44276-026-00249-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:48:17Z","timestamp":1789451297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44276-026-00249-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["249"],"URL":"https:\/\/doi.org\/10.1038\/s44276-026-00249-3","relation":{},"ISSN":["2731-9377"],"issn-type":[{"value":"2731-9377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]},"assertion":[{"value":"22 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"BTE is an employee of MyCural Therapeutics. Other authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The in vivo experiments were approved by the Stockholm Regional Ethics Committee (ethical permits ID: 5163-2019 and 4356-2024), appointed and under the control of the Swedish Board of Agriculture and Swedish Court. National and European Union (EU) regulations were followed (SFS 2018:1192, SFS 2019:66, and SFS 2007:488 and EU Directive 2010\/63\/EU).","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from all participants, and all patient tissue collection was carried out with IRB approval, Etikpr\u00f6vningsmyndigheten. Diary number (registration): 2009\/1369-31\/1 and 2022-07254-01.","order":3,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"46"}}