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Convection-enhanced delivery of dexamethasone in glioma models suppresses myeloid inflammation while avoiding systemic toxicities

GSE326006 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing 21 samples Submitted 2026/07/07 Platform GPL34295Platform GPL24247
Summary
Dexamethasone is widely used to control cerebral edema and inflammation in glioblastoma, but its benefits are limited by systemic toxicities and adverse prognostic associations. We evaluated local administration of dexamethasone via convection-enhanced delivery (CED) to maximize intratumoral anti-inflammatory effects by increasing local corticosteroid exposure while minimizing systemic exposure. In two glioma mouse models, continuous intraparenchymal infusion of dexamethasone was well tolerated with no adverse effects. Pharmacokinetic analyses supported preferential intratumoral distribution and reduced systemic exposure with CED compared with systemic dosing. Single-nucleus RNA sequencing (snRNA-seq) and immunohistochemistry showed attenuation of glioma-associated inflammation with downregulation of reactive microglial/macrophage programs and reduced tumor-infiltrating myeloid cells with a morphology consistent with a less activated state. Experiments in human induced pluripotent stem cell (iPSC)–derived microglia confirmed that dexamethasone directly suppresses inflammatory gene expression, indicating a conserved mechanism across species. This inflammatory suppression was recapitulated in both immortalized microglial (HMC3) and macrophage (THP1) cell lines. These findings suggest that localized dexamethasone delivered by CED reprograms the glioma immune microenvironment and achieves control of inflammation without the systemic adverse effects associated with standard systemic dexamethasone therapy. This clinically translatable strategy may improve symptom management and provide a platform for integrating local immunomodulation with future glioblastoma therapies.
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Direct links to NCBI, no account and no request form: the whole study as GSE326006_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 21 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1442811 and SRA study SRP686740. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
Control ×6 Systemic Dexamethasone ×3 CED Dexamethasone ×3 Dexamethasone ×3 LPS ×3 LPS+Dexamethasone ×3

Supports a between-group comparison across 21 samples.

6 replicated groups read from 21 sample titles; they account for 21 of them. Check it against the sample list below before relying on it.

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