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Through spatial transcriptomics combined with histological analyses, we delineated the spatial determinants that limit viral dissemination following oncolytic virus administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified B\u2011cell lymphoma\/leukemia 10 (BCL10) as a key suppressor of sustained viral replication. Viral infection activated the BCL10\u2013NF-\u03baB pathway, triggering paracrine secretion of interleukin-8 (IL-8) from infected tumor cells. Interleukin-8 induced senescence and fibrotic remodeling in neighboring uninfected cells, forming a previously unrecognized Tumor Self-Rampart (TSR)\u2014a concentric barrier of senescent and fibrotic tumor cells that spatially confines viral propagation. Tumor Self-Rampart was validated in both PDX and patient tumors. Interleukin-8 blockade with Reparixin or peri-dosing glucocorticoids effectively disrupted TSR formation, prolonged viral persistence, and enhanced therapeutic efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Glioblastoma mounts a spatial self-protective defense through IL-8\u2013driven TSR formation that restricts oncolytic virus spread. Interleukin-8 functions as both a pharmacodynamic biomarker and a therapeutic target, and its inhibition provides a rational strategy to overcome resistance and optimize GBM virotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf276","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T12:31:16Z","timestamp":1764592276000},"page":"643-658","source":"Crossref","is-referenced-by-count":2,"title":["Interleukin-8-induced tumor self-rampart spatially confines oncolytic virotherapy in glioblastoma"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-126X","authenticated-orcid":false,"given":"Shan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai,","place":["China"]},{"name":"National Center for Neurological Disorders , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houshi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai,","place":["China"]},{"name":"National Center for Neurological Disorders , Shanghai,","place":["China"]},{"name":"Neurosurgical Institute, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai,","place":["China"]},{"name":"National Center for Neurological Disorders , Shanghai,","place":["China"]},{"name":"Neurosurgical Institute, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfen","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica, Chinese Academy of Sciences ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai,","place":["China"]},{"name":"National Center for Neurological Disorders , Shanghai,","place":["China"]},{"name":"Neurosurgical Institute, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital, Fudan University , Shanghai,","place":["China"]},{"name":"National Center for Neurological Disorders , Shanghai,","place":["China"]},{"name":"Neurosurgical Institute, Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of 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