Abstract C080: Glioma cell-mediated hyper-thrombotic tumor microenvironment drives glioblastoma growth

Abstract Cancer-related thrombosis is the second leading cause of death for cancer patients, including those with glioblastoma (GBM), the most common primary malignant brain tumor. Patients with GBM have a 30% risk of venous thromboembolism (VTE). High platelet counts, and increased platelet reactivity are associated with poor clinical outcomes in many cancers. While platelets are known to promote progression of tumors, the mechanisms by which these changes in platelet reactivity act as a driver for GBM progression is unknown. Our previous work demonstrated that a subpopulation of glioma cells activates platelets to promote GBM cell growth by intrinsically producing thrombin via a cell intrinsic functional coagulation cascade. These findings provided evidence that glioma cells can readily execute a highly liver-specific gene expression program that contributes to a hyper-thrombotic state in the GBM tumor microenvironment (TME). We now demonstrate thrombin and platelet expression in GBM patient specimen creates a hyper-thrombotic GBM tumor-microenvironment and that GBM patient platelets have increased reactivity compared to healthy patients. Further, genetic targeting of the intrinsic coagulation cascade, via knockdown of coagulation factor 11 (F11) and coagulation factor 12 (F12), reduces glioma cell growth and tumor formation while also decreasing the ability for glioma cells to activate platelets, subsequently decreasing the hyper-thrombotic state seen in the GBM tumor microenvironment. Our observations suggest that glioma cells execute a cell intrinsic coagulation mechanism to contribute to the hyper-thrombotic tumor-microenvironment seen in GBM and may shed light onto mechanisms of cancer associated thrombosis in not only GBM, but also other malignancies. Citation Format: George Bukenya, Anthony Sloan, Craig Horbinski, Anirban Sen Gupta, Scott Cameron, Justin Lathia. Glioma cell-mediated hyper-thrombotic tumor microenvironment drives glioblastoma growth [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C080.