Microglia-glioblastoma crosstalk mediates glioblastoma invasion at the far infiltration zone
Year: 2026
Type: article
Abstract: Glioblastoma (GB) cells infiltrate the brain parenchyma and colonize distant regions, driving recurrence and therapy resistance. Here, we examined dynamic microglial responses to infiltrating tumor cells during GB progression. Three-photon imaging in an autochthonous, immunocompetent GB mouse model enabled visualization of microglia-GB interactions at the far infiltration zone (FIZ) in the corpus callosum (CC). GB infiltration speed varied by anatomical location and tumor microtube (TM) number. Microglia increased surveillance in sparsely infiltrated areas but reduced it with higher GB density, revealing a biphasic response. Directional migration toward GB cells was restricted to microglial subsets within a defined spatial range, indicating heterogeneous reactivity. CX3CR1 deficiency enhanced microglial reactivity while limiting GB cell migration. Microglia depletion with the CSF1R inhibitor PLX5622 reduced GB cell migration and constrained TM plasticity. Thus, microglia respond to GB cell infiltration in a stage-dependent manner and critically modulate dissemination at the FIZ.
Source: Immunity
Authors: Felix C. Nebeling, Falko Fuhrmann, Manuel Mittag, Fabrizio Musacchio, Henrike Antony, Nala Gockel, Lea L. Friker, Sonia Leonardelli, Severin Filser, Deli A., Miriam Stork, Daniele Bano, Torsten Pietsch, Frank A. Giordano, Qihui Zhou, Simona Parrinello, Michael Hölzel, Ulrich Herrlinger, Paolo Salomoni, Martin Fuhrmann
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Land Nordrhein-Westfalen, Deutsches Krebsforschungszentrum, Wilhelm Sander-Stiftung, Deutsche Forschungsgemeinschaft, Deutsches Zentrum für Neurodegenerative Erkrankungen, Deutsche Krebshilfe, Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen, World Cancer Research Fund, European Research Council
OpenAlex ID: W7147174006