Tumor Associated Neutrophils Extend NETs To Spatially Drive Necroptosis In Glioblastoma

High tumoral necrotic volume on clinical MRI is an independent biomarker of poor long-term survival in glioblastoma, and it is radiogenomically driven by TP53, PTEN, and NF1 co-mutations.

• Why it matters: Glioblastoma necrosis is linked to therapeutic resistance and dismal prognosis, but the radiogenomic drivers and spatial immune architecture that orchestrate active tumor necrosis were unclear.
• What they did: The study integrated MRI radiomics with public genomic datasets (n=3,639), single-cell spatial transcriptomics, and high-resolution protein immunofluorescence in a co-mutant murine model, mapping necrotic niches and their chemokine signals.
• The result: TypeNec cells recruit tumor-associated neutrophils to form NETs and drive a feed-forward HMGB2-mediated necroptosis cascade, which anti-inflammatory compounds could dismantle; an HMGB2high signature predicts a high-risk, myeloid-rich immunosuppressive microenvironment in glioblastoma patients.