Defense Date

2022

Document Type

Thesis

Degree Name

Master of Science

Department

Biochemistry

First Advisor

Tomasz Kordula

Abstract

Glioblastoma Multiforme has been shown to be one of the deadliest primary brain cancers. One of the reasons why GBM is so deadly, is a unique immunosuppressive tumor microenvironment that promotes GBM growth and progression. Both astrocyte and microglia have been implicated in immunosuppression. In this study, we explored the role of Interferon Regulatory Factor 1 (IRF-1) in astrocytes and glioma cells on the growth of spontaneous glioma tumors. IRF-1 is regulated by the JAK/STAT pathway and induces expression of Programmed death ligand 1 (PD-L1). PD-L1 downregulates immune responses to glioma. We found that IRF-1 had no effect on spontaneous glioma generation nor growth. We also discovered that PD-L1 expression was downregulated in glioma cells. There was still high PD-L1 expression in microglia. Interestingly, we found that tumor vascularization was significantly decreased in animals lacking IRF-1 expression in astrocytes. This has been associated with the loss of CD31 positive staining in endothelial cells as well as the loss of AQP4 expression. Our data suggests that astrocytic IRF-1 may control tumor vascularization via regulating astrocytic endfeet.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-2-2022

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