The Role of Annexin A1 Expression in Glioblastoma-Associated Astrocytes

The project consists of three specific aims: 1) Establish the effects of ANXA1 on astrocytes and glioma-reactive T-cells by inactivating Anxa1 in a GBM mouse model and quantifying astrocyte NF-kB and inflammasome activity and T-cell dysfunction. 2) Determine if ANXA1+ astrocytes influence survival in murine and human high-grade glioma by measuring survival in glioma-bearing mice with astrocyte-specific Anxa1 inactivation (alone, with anti-PD1, and with Mlkl inactivation) and defining the link between astrocyte ANXA1 expression and clinical outcomes in Veteran GBM patients. 3) Elucidate the role of ANXA1+ astrocyte interactions with GBM-associated macrophages by performing cell barcoding RABID-seq on GBM tissue, detecting mediators of interactions between ANXA1+ astrocytes and TAMs, and validating clinical relevance through multivariate survival analysis, immunofluorescence of GBM autopsies, and survival analysis of glioma-bearing mice.