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To address this barrier, extracellular vesicles (EVs) harvested from oHSV\u20101\u2010infected GSCs (EVOV) were evaluated for their immunomodulatory capacity by priming peripheral blood mononuclear cells (PBMCs)\n                    <jats:italic>ex vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In GSC\u2010PBMC organoids analysed by single\u2010cell RNA sequencing, IFN\u2010response and antigen\u2010presentation programs were induced in both immune and tumour compartments, despite the GSC state. EVOV organoid transcriptome associated with patient tumour antigen\u2010processing programs linked to improved clinical outcome, and EVOV immunopeptidomics identified candidate biomarker peptides that were also detected in patient immunopeptidomes from the clinical\u2010trial cohort. In PBMC\u2010engrafted NOD\n                    <jats:italic>scid<\/jats:italic>\n                    gamma mice bearing intracranial GSC xenografts, EVOV delivery increased circulating interferon (IFN) levels and enhanced systemic activation of T\u2010cell subsets, while spatial transcriptomics revealed recruitment of peripheral immune cells to the tumour, accompanied by reprogramming of GSC states. Blocking vesicle\u2010associated major histocompatibility complex I (MHC\u2010I) attenuated EVOV\u2010driven PBMC cytotoxicity against GSCs, supporting an MHC\u2010I peptide\u2010dependent mechanism of immune priming and a vaccine\u2010 or adjuvant\u2010like, non\u2010infectious, vesicle\u2010based immunotherapeutic strategy.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70389","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:28:22Z","timestamp":1792646902000},"source":"Crossref","is-referenced-by-count":0,"title":["Oncolytic Virus\u2010Engineered Extracellular Vesicles Rewire Glioblastoma Immunity"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1777-6548","authenticated-orcid":false,"given":"Klaudia","family":"Kiel","sequence":"first","affiliation":[{"name":"Tumor Microenvironment Laboratory Mossakowski Medical Research Institute Polish Academy of Sciences  Warsaw Poland"},{"name":"Translational 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