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.
Show 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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