Targeting a Granulocytic/Microbiome Axis Reverses Glioblastoma Progression via Intranasal Cannabidiol

Wang, L. P.; Bhandari, B.; Naeini, S. E.; Earwood, J. T.; Marshall, B.; Wakade, C.; Yu, J. C.; Arbab, A. A.; Lopes Salles, E.; Baban, B.

doi:10.64898/2026.07.12.737962

bioRxiv · 10.64898/2026.07.12.737962

Targeting a Granulocytic/Microbiome Axis Reverses Glioblastoma Progression via Intranasal Cannabidiol

Wang, L. P.·Bhandari, B.·Naeini, S. E.·Earwood, J. T.·Marshall, B.·Wakade, C.·Yu, J. C.·Arbab, A. A.·Lopes Salles, E.·Baban, B.

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Abstract

Mucosal cannabidiol formulations are known regulators of the glioblastoma microenvironment, yet the underlying origin point triggering this stroma-remodeling efficacy remains entirely unknown. Here, by mapping innate cell trafficking pathways, we define a novel baseline neuro-immune-microbiome axis in orthotopic glioblastoma, characterized by diverse microbial communities, likely seeded via blood-brain barrier disruption, paired with dense infiltration of host mast cells and mature, crystalloid-containing eosinophils. Localized intranasal administration of a synthetic cannabidiol formulation achieved striking therapeutic efficacy, driving dramatic tumor regression. Mechanistically, high-throughput 16S rRNA sequencing and quantitative flow cytometry revealed this progression was subverted by taming the tumor ecosystem; cannabidiol restricted chaotic microbial diversity, selectively filtering the landscape toward Delftia and depleting Archaea, while simultaneously suppressing hyper-inflammatory host mast cell and eosinophil populations. This study builds upon established innate trafficking frameworks to present the first therapeutically targetable stromal-microbial axis in neuro-oncology.

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Wang, L. P., Bhandari, B., Naeini, S. E., Earwood, J. T., Marshall, B., Wakade, C., Yu, J. C., Arbab, A. A., Lopes Salles, E., Baban, B.. 2026-07-13. Targeting a Granulocytic/Microbiome Axis Reverses Glioblastoma Progression via Intranasal Cannabidiol. https://doi.org/10.64898/2026.07.12.737962

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