STING-induced blood-brain barrier opening combined with radiotherapy potentiates antitumor response in a high-grade glioma model - PubMed
6 days ago
- #glioblastoma
- #blood-brain barrier
- #STING pathway
- Radiation therapy (RT) is standard for glioblastoma but not curative.
- Combining STING agonist 8803 with RT showed 80% long-term survival in CT-2A glioma model but not in QPP8v model.
- Therapeutic effect was maintained in Sting-/- CT-2A cells, indicating immune system's role.
- Single-cell RNA-Seq identified increased Nos2 in inflammatory tumor-associated macrophages, but effect persisted in Nos2-/- mice.
- 8803 altered BBB by changing Pecam and Cd147 pathways in endothelial cells, inducing bihemispheric BBB opening for up to 24 hours.
- STING activation peaked 72-96 hours post-8803 administration, visualized via [18F]-FLT PET.
- Combination therapy triggers antiglioma immune reactivity and BBB opening, suggesting potential for clinical trials in glioblastoma.