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ResearchIn-Press PreviewInflammationOncology Open Access | 10.1172/JCI200550

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

Nathaniel W. Rolfe,1 Nicholas B. Dadario,1 Liang Lei,1 Anthony Tang,1 Misha Amini,1 Damian E. Teasley,1 Nkechime Ifediora,2 Peter Chabot,1 Nathan J. Winans,1 Nina Yoh,1 Julia Furnari,1 Corina Kotidis,1 Clara H. Stucke,1 Nivia M. Urena,3 Yanping Sun,4 Abby Brand,2 Ashwin Viswanathan,2 Pavan Upadhyayula,1 Michael G. Argenziano,1 Colin P. Sperring,1 Nadine Khoury,1 Nelson Humala,1 Shikun Wang,5 Justin Neira,1 Peter A. Sims,6 Brian J. Gill,1 Peter Canoll,2 and Jeffrey N. Bruce1

1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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1Department of Neurological Surgery, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

2Department of Pathology and Cell Biology, Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

3Insititue of Comparative Medicine (ICM), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

4Oncology Precision Therapeutics and Imaging Core (OPTIC), Columbia University Irving Medical Center/NY- Presbyterian Hospital, New York, United States of America

5Department of Biostatistics, Columbia University Irving Medical Center, New York, United States of America

6Department of Systems Biology, Columbia University Irving Medical Center, New York, United States of America

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Published August 18, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI200550.
Copyright © 2026, Rolfe et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 18, 2026 - Version history
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Abstract

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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