Published in @NatureCancer (May 2025), Kang et al. uncover a novel microglia-driven mechanism governing GBM transition from bulk tumor growth to invasive spread. They reveal that microglia, guided by the protein plexin-B2, undergo a remarkable transformation—initially forming protective “glial nets” around small tumor infiltrates, and subsequently reorganizing into structured pathways called “oncostreams” that actively facilitate collective tumor cell migration. Plexin-B2 is central to this invasive process, orchestrating tumor cell alignment, resolves cell collisions, and remodels the ECM into organized tracks for GBM invasion. This study provides critical new insights into GBM’s complex TME, positioning microglia as critical architects of tumor invasiveness—opening potential new therapeutic strategies that target stromal interactions to limit GBM progression. @MountSinaiNeuro @IcahnMountSinai @SinaiBrain