Defne Bayik, PhD

Glioblastoma (GBM) is the most frequent and deadly malignant brain tumor. Escape from the body’s immune response is a critical factor that makes GBM untreatable. One promising anti-GBM strategy is to augment the tumor-fighting capacity of immune cells. CD8+ T cells have the potential to kill tumors, but cancers make them not function properly. Strategies that aim to prevent this process have not been successful in GBM yet. We recently found that a molecule named dipeptidyl peptidase 4 (DPP-4) is present on dysfunctional T cells at high levels. Furthermore, we observed that DPP-4 prevents CD8+ T cells from killing tumors. In this application, we aim to determine how DPP-4 reprograms T cells to a nonfunctional state. DPP-4 inhibitors are commonly used by patients with diabetes. We seek to repurpose these drugs in combination with existing immune-activating strategies to improve T cell response against GBM. Collectively, these studies will define DPP-4 as a new treatment target in GBM.