TMET-25. TNFR1 Knockdown Sensitizes Glioblastoma Cells to Cell Death

Abstract BACKGROUND Glioblastoma (GBM) is the brain tumor with poor prognosis, despite advances in surgery, radiation, and chemotherapy. Tumor necrosis factor (TNF) signaling, particularly through TNF receptor 1 (TNFR1), has been associated with inflammation and tumor biology in GBM. However, its precise functional role in tumor maintenance and therapeutic resistance remains incompletely understood. METHODS To investigate the role of TNF in GBM, we conducted RNA sequencing following TNFR1 knockdown in GBM cells and assessed changes in gene expression. We also conducted in vitro and in vivo experiments to examine the functional impact of TNFR1 modulation on tumor behavior. RESULTS TNFR1 knockdown resulted in decreased tumor cell proliferation and increased cell death. Transcriptomic profiling revealed changes in gene expression, including alterations in pathways related to oxidative stress and cell death. Additionally, retrospective analysis of clinical cases from our institution showed that high TNFR1 expression was associated with poorer prognosis in patients with GBM. Notably, several cell death-related genes that were altered in vitro and in vivo experiments showed expression patterns that correlated with TNFR1 levels in clinical tumor samples. CONCLUSION These findings suggest that TNFR1 may play a critical role in maintaining GBM cell survival through modulation of regulated cell death pathways. Targeting this signaling axis could provide a therapeutic advantage by sensitizing tumor cells to cell death. Further investigation is ongoing to validate these observations and explore their clinical relevance.