Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence

Hadeesha Piyadasa; Benjamin Oberlton; Mikaela K. Ribi; Ke Xuan Leow; Jolene S. Ranek; Inna Averbukh; Meelad Amouzgar; Candace C. Liu; Davide G. Franchina; Noah F. Greenwald; Erin McCaffrey; Rashmi Kumar; Selena Ferrian; Albert G. Tsai; Ferda Filiz; Christine Camacho Fullaway; Marc MB Bosse; Sricharan Reddy Varra; Alex Kong; Cameron Sowers; Melanie Hayden Gephart; Pablo Nunez Perez; Enjun Yang; Mike Travers; Michael J. Schachter; Samantha Liang; Mariarita Santi; Samantha L. Bucktrout; Pier Federico Gherardini; John Connolly

doi:10.1016/j.ccell.2025.11.006

Cancer BiologyCancer CellDec 11, 2025

Peer-reviewed journal article

Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence

Hadeesha Piyadasa iD, Benjamin Oberlton, Mikaela K. Ribi iD, Ke Xuan Leow, Jolene S. Ranek iD, Inna Averbukh iD, Meelad Amouzgar iD, Candace C. Liu iD, Davide G. Franchina iD, Noah F. Greenwald iD, Erin McCaffrey iD, Rashmi Kumar iD, Selena Ferrian iD, Albert G. Tsai iD, Ferda Filiz, Christine Camacho Fullaway iD, Marc MB Bosse iD, Sricharan Reddy Varra iD, Alex Kong iD, Cameron Sowers, Melanie Hayden Gephart iD, Pablo Nunez Perez iD, Enjun Yang iD, Mike Travers, Michael J. Schachter, , Michael Angelo iD

Abstract

Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) evolution, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma (PXA), while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Longitudinal samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T-cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206+ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study opens new avenues for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.

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