Preliminary data from our lab shows that vascular endothelial cells (vECs) mount remarkably potent innate responses to cell-free DNA, which is well in accordance with their role as sentinels of the blood. However, little is known about how the contribution of innate endothelial responses to the inflammatory landscape of the tumor microenvironment. We are using primary endothelial-tumor cell co-culture, Next Generation RNA-sequencing profiling, RNAi/CRISPR/Cas9-mediated gene deletion, animal models of cancer and human tumor bio-samples to explore the role of vECs as bona fide effectors of the innate response to cancer.