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Mapping immunotherapy distribution by multimodality imaging might be a biomarker that could aid tumor monitoring and guide therapy development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To assess drug delivery, we developed a MRI-lightsheet microscopy platform (MR-LSM) to monitor immunotherapy at the cellular level in two immunocompetent glioma models (Gl261, SB28). The atezolizumab (PD-L1 inhibitor) subgroup of the multicenter N2M2\/NOA20 trial in MGMT unmethylated GBM patients was assessed by CNN analysis and correlated to progression-free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In contrast to the conventional Gl261 glioma model, SB28 gliomas are characterized by poor immunogenicity and resistance to Toll-like receptor (TLR) 7 targeted therapy delivered by CDNP-R848 nanoparticles. SB28 resistance is driven by microvascular pathology, vasogenic edema, and drug off-targeting to peritumoral edema and white matter tracts. Vascular endothelial growth factor (VEGF) inhibition in conjunction with irradiation and dual immunotherapy (DIR) targeting innate (CDNP-R848) and adaptive immunity (anti-CTLA-4) breaks resistance, increases survival, and reverses drug off-targeting. Mechanistically, tumor control is orchestrated by vascular normalization, enhanced CD8+ T cell influx, and a proinflammatory shift of myeloid cells along with strong IL-12\/IL-13 upregulation. In a translational analysis of the multicenter N2M2\/NOA20 trial, we validate that edema and microvascular pathology are associated with poor prognosis in glioblastoma patients treated with checkpoint immunotherapy and that patients without edema have increased PFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>. We develop a customizable imaging platform to map drug delivery to glioma with broad applicability in neuroscience and neuro-oncology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf295","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T12:33:25Z","timestamp":1767011605000},"page":"1038-1052","source":"Crossref","is-referenced-by-count":2,"title":["Multimodality mapping of immunotherapy distribution as a predictive marker in glioma"],"prefix":"10.1093","volume":"28","author":[{"given":"Jonas G","family":"Scheck","sequence":"first","affiliation":[{"name":"Neuroradiology Department, University Hospital Heidelberg , Heidelberg,","place":["Germany"]},{"name":"Clinical Cooperation Unit Translational Radiation Oncology, German Cancer Consortium (DKTK), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ) , 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