Federal Project Grant Award Summary

The National Cancer Institute (National Institutes of Health) awarded The Trustees of The University of Pennsylvania a Project Grant of $594,899 under the Cancer Treatment Research program (CFDA 93.395) to conduct basic and translational research on glioblastoma (GBM) immunotherapy. The five-year research initiative, initiated July 6, 2026 and concluding June 30, 2031, focuses on understanding the vascular regulation of macrophage function in brain tumors and developing efficient immunotherapies for primary brain cancers. The research team will employ single-cell transcriptome analysis and molecular biology techniques to investigate how tumor endothelial cells produce osteopontin through a TWIST1-mediated mechanism that promotes immunosuppressive macrophage polarization. Key deliverables include characterization of endothelial cell-macrophage interactions, evaluation of TWIST1 pharmacological inhibition as a therapeutic strategy, and assessment of combination approaches pairing TWIST1 inhibition with chimeric antigen receptor (CAR) T cell immunotherapy to overcome GBM resistance to immunological treatment.

This research addresses a critical clinical need, as glioblastoma remains the most common and aggressive primary brain malignancy in adults with limited treatment options and median overall survival of 14–18 months. The project generates foundational knowledge applicable to reversing macrophage-mediated immunosuppression in the tumor microenvironment and may enable development of combination immunotherapy protocols that enhance T cell infiltration and activation in brain tumors. Research outcomes will be disseminated through scientific publications and may inform future clinical trials and therapeutic development initiatives.