Reactive astrocyte-like states confer radiation resistance in glioblastoma

This is the authors' abstract. We don't add key points for this paper.

: Glioblastoma is the most malignant and therapy-resistant brain tumour in adults. Resistance is often attributed to pervasive intra-tumour heterogeneity, including the presence of neurodevelopmental and injury-like tumour cell states. However, whether or how cell state impacts acute treatment responses remains poorly understood. Here, we used single-cell mass cytometry with signalling resolution in patient-derived and mouse models to characterise the tumour subpopulations that persist immediately following radiation, the cornerstone of current standard-of-care therapy. We find that slow-cycling, reactive astrocyte-like cells become selectively enriched post-radiotherapy through efficient DNA repair and reduced apoptotic signalling. Functional perturbation and digital pathology approaches further revealed that astrocyte-like states are induced by tumour-derived BMP signalling within spatially segregated niches. These findings identify cell state as a key determinant of radiation response and suggest that glioblastoma co-opts neurodevelopmental programmes to actively maintain reservoirs of resistant subpopulations.