Microglia-glioblastoma crosstalk mediates glioblastoma invasion at the far infiltration zone

2026/03/31 by Felix C. Nebeling, Falko Fuhrmann, Manuel Mittag +17 · 3 voices · 1 citation
Medicine · Neuroscience · #Glioma Diagnosis and Treatment #Neuroinflammation and Neurodegeneration Mechanisms #Barrier Structure and Function Studies

paper · doi:10.1016/j.immuni.2026.03.010

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.

Citations

• Neurofibromatosis-1 Heterozygosity Increases Microglia in a Spatially and Temporally Restricted Pattern Relevant to Mouse Optic Glioma Formation and Growth
• CX3CR1 Deficiency Alters Microglial Activation and Reduces Beta-Amyloid Deposition in Two Alzheimer's Disease Mouse Models

Cited by

• OMIO: A policy-driven Python library for reproducible microscopy image I/O

Discussions

• Great new work from our lab: #Microglia #glioblastoma interaction in vivo analyzed deep in the corpus callosum wirh #3photon microscopy by @felixnebeling.bsky.social doi.org/10.1016/j.im... #neuros [bsky, 13 points, 1 comments]
• 🚨New paper from the lab🚨 Felix shows that #microglia shape #glioblastoma invasion at the far infiltration zone. Using in vivo #3photon #imaging, he finds dynamic responses & shows that manipulation [bsky, 7 points, 1 comments]
• Microglia-glioblastoma crosstalk mediates glioblastoma invasion at the far infiltration zone. Felix Nebeling et al. @cp-immunity.bsky.social (2026). DOI: doi.org/10.1016/j.im... [bsky, 1 points, 0 comments]

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