Abstract 6362: Characterization of therapeutic effects in glioblastoma through integrated spatial single-cell multiome profiling of longitudinal samples: Unveiling clinically relevant subtypes of pathological changes

Abstract Glioblastoma remains a highly malignant, inevitably recurring brain tumor with dismal prognosis. Tumor progression is influenced by cellular interactions between the tumor and its microenvironment, yet quantitative data on these interactions, particularly under standard of care therapy, remains sparse. We utilized spatial, single-cell, multiome profiling to map therapy-induced changes in the architecture of >700 paired glioblastoma samples derived from 101 patients at diagnosis and recurrence. This approach categorized patients into groups reflecting specific evolutionary responses to therapy, with implications for prognosis and treatment. Favourable outcomes were linked to shifts towards enriched perivascular, oligodendrocyte-progenitor-like niches with deep tissue infiltration of activated immune cells, whereas poor outcomes correlated with shifts towards an immunosuppressive mesenchymal environment with poor immune infiltration. Finally, while mutations in EGFR/PTEN, or MGMT-promoter methylation influenced tumor evolution, we also identified a defined subset of patients that were more responsive to lomustine after early recurrence. Our findings offer a framework to stratify patient treatment based on tumor and microenvironmental evolution. Citation Format: Maxime Vanmechelen, Pouya Nazari, Jan Beckervordersandforth, Daphne Leunissen, Basiel Cole, Brecht Decraene, Yanti De Visser, Gautam Shankar, Maikel Verduin, Daniele Pantano, Carmen Bravo Gonzalez-Blas, Chiara Caprioli, Sien Bevers, Tom Moors, Jayesh Telang, Ivey Sebasstian, Julie Messiaen, Yannick Van Herck, Emma Geens, Danielle Eekers, Annelies Claeys, Marleen Derweduwe, Axel Zur Hausen, Francesca Bosisio, Frank Weyns, Thomas Daenekindt, Peter Van Eyken, Mieke Govers, Ferdinand Mennens, Koos Hovinga, Steven De Vleeschouwer, Paul Clement, Martijn Broen, Marc Vooijs, Raf Sciot, Asier Antoranz, Jon Pey, Ernst-Jan Speel, Ann Hoeben, Frederik De Smet. Characterization of therapeutic effects in glioblastoma through integrated spatial single-cell multiome profiling of longitudinal samples: Unveiling clinically relevant subtypes of pathological changes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6362.