{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:45:50Z","timestamp":1791924350154,"version":"4.3.4"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"10","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>No curative options are available for medulloblastoma (MB) in the relapse setting. The tumor microenvironment (TME) influences progression and therapy response, presenting a promising target for therapeutic advances. Prior single-cell analyses have characterized the cellular components of the TME but lack spatial context. We hypothesize that spatial architecture, beyond cell composition, influences tumor progression and treatment outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed spatial transcriptomic sequencing on 18 pediatric MB samples obtained at diagnosis, including two matched diagnosis-relapse pairs. Samples at diagnosis were stratified into high- and standard-risk groups. Spatial data were analyzed for spatial proximity to other cell types, cell-cell communication networks, and expression of cell cycle dormancy signatures. Findings were validated using immunohistochemistry in the same cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analyses revealed intertumoral and intratumoral heterogeneity within the TME, comprising tumor-associated astrocytes (TAAs), macrophages (TAMs), stromal components, and distinct subpopulations of MB cells at different stages of neuronal differentiation and cell cycle progression. We identified dense regions of quiescent progenitor-like MB cells enriched in patients with high-risk (HR) features and an increase in TAAs, TAMs, and dysregulated vascular endothelium following relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study presents novel insights into the spatial architecture and cellular landscape of the MB-TME, highlighting differential spatial patterns correlating with HR features. Future studies should evaluate their role in relapse and therapy resistance and may lead to uncovering novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-01195","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:59:07Z","timestamp":1791921547000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Medulloblastoma Spatial Transcriptomics Reveals Tumor Microenvironment Heterogeneity With High-Density Progenitor Cell Regions Correlating With High-Risk Disease"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4206-8580","authenticated-orcid":true,"given":"Franklin","family":"Chien","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Emory School of Medicine, Atlanta, GA"},{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0145-7320","authenticated-orcid":true,"given":"Marina E.","family":"Michaud","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory School of Medicine, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojtaba","family":"Bakhtiari","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory School of Medicine, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2844-2075","authenticated-orcid":true,"given":"Chanel","family":"Schroff","sequence":"additional","affiliation":[{"name":"Department of Pathology, NYU Langone Health and Grossman School of Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-0917","authenticated-orcid":true,"given":"Matija","family":"Snuderl","sequence":"additional","affiliation":[{"name":"Department of Pathology, NYU Langone Health and Grossman School of Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Velazquez Vega","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children's Healthcare of Atlanta and Emory School of Medicine, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobey J.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory School of Medicine, Atlanta, GA"},{"name":"Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, 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