{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:12Z","timestamp":1790618232548,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272757"],"award-info":[{"award-number":["82272757"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7254409"],"award-info":[{"award-number":["7254409"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aims to systematically dissect how MYCN amplification shapes the immunosuppressive tumor microenvironment (TME) in high\u2010risk neuroblastoma, elucidating key mechanisms underlying immune evasion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed an integrated multi\u2010omics analysis of bulk RNA\u2010seq (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009721), single\u2010cell RNA\u2010seq (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099), proteomic data (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200949) and spatial transcriptomics (Visium, with external validation in melanoma). Analyses included unsupervised clustering, cell\u2013cell communication inference, transcriptional regulatory network reconstruction, and spatial proximity assessment to map the immune landscape.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A distinct molecular subtype (Class C), defined by MYCN amplification and poor prognosis, exhibited a comprehensive \u201cimmune desert\u201d phenotype characterized by low immune scores and minimal leukocyte infiltration. Single\u2010cell analysis confirmed significant depletion of T and B lymphocytes within the Class C TME. Dysregulated transcriptional networks were identified, including upregulation of REL and EOMES in T cells\u2014with EOMES potentially driving exhaustion via regulation of Transient Receptor Potential (TRP) genes, and REL inhibition enhancing cytotoxic function in\u00a0vitro. A unique immunosuppressive B\u2010cell subset (B7) engaged in enhanced crosstalk with exhausted T cells and harbored a MYC\u2010centered network linked to cell cycle dysregulation and poor survival. Spatial transcriptomics revealed significant proximity between B7\u2010active regions and Treg\/exhaustion\u2010enriched areas, externally validated in melanoma. Proteomic data validated elevated REL expression in MYCN\u2010amplified tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This work delineates the immunosuppressive architecture of MYCN\u2010driven neuroblastoma, revealing novel regulatory nodes within specific lymphocyte compartments. Integrating single\u2010cell, spatial, and proteomic evidence, we propose REL inhibition as a therapeutic candidate, the EOMES\/TRP axis as a bioinformatically supported hypothesis, and the B7\/MYC hub as a hypothesis supported by transcriptomic and spatial evidence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71054","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:59:27Z","timestamp":1788253167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Genomic and Proteomic Analysis Reveals T\u2010B Lymphocyte Signatures in the\n                    <scp>MYCN<\/scp>\n                    Driven \u201cImmune Desert\u201d of Specific Neuroblastoma Subtypes"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3750-8417","authenticated-orcid":false,"given":"Jia\u2010Jian","family":"Hu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9727-5005","authenticated-orcid":false,"given":"Wen\u2010Juan","family":"Kang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Tong","family":"Hu","sequence":"additional","affiliation":[{"name":"Acupuncture Department Guang'anmen Hospital, China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0985-235X","authenticated-orcid":false,"given":"Ye\u2010Xiong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1542-0828","authenticated-orcid":false,"given":"Feng\u2010Ju","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology in Tianjin, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute &amp; Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology and Department of Radiation Oncology National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010022\u201000643\u2010z"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010023\u201002913\u20109"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102023\u2010007174"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.011"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2025.04.013"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.12.008"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.05.025"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2022.06.013"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201051337\u20102"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.8.10.8358"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6125"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100523\u2010y"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2957"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.19.00072"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100657"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33423"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1040"},{"key":"e_1_2_12_19_1","doi-asserted-by":"crossref","unstructured":"L. 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