Ryan Getler

Glioblastoma (GBM) is a very aggressive and fast-growing brain cancer, accounting for nearly half of all brain cancers with a low survival rate. In the context of radiation therapy the immune system is stimulated, though in GBM cells this is not the case. Studying how the immunosuppressive mechanisms work inside GBM will allow scientists to understand how to inhibit these functions and allow cancer treatments to work more effectively. The research at the Vanpouille-Box lab aims to specifically understand how GBM survives and resists immunogenicity after radiation therapy treatment. The methods used to study these effects consist of immunotherapy to inhibit functions of pro-tumor proteins. Immunofluorescent staining was also used to quantify lipid content to understand the effects of metabolic changes. FASN, an enzyme that benefits the pooling of lipids in the cell for energy was inhibited to see how lipid content would be affected. It was found that the inhibitors for FASN: TVB and BI, helped significantly reduce lipid content in GBM cells post-radiation therapy. Lipids in GBM cells are stored in lipid droplets (LD), and a presumed mechanism was the  synthesis of Prostaglandin E2 (PGE2). Detecting the presence of PGE2 in irradiated GBM cells, it was found that RT induce the secretion of Prostaglandin E2 leading to immunosuppressive effects by the disfunction of T cells.  Understanding these metabolic mechanisms is the key to making cancer treatments more effective in killing GBM. As the Vanpouille-Box lab further looks for mechanisms of tumor resistance, immunosuppressive signals between Timp1 and CD63 which are overexpressed in context of radiation therapy, stand promising for understanding more about GBM resistance.