Although multiple mechanisms could play a role in the transition of an endothelial cell from a physiological to a pathological phenotype, the observation that pharmacological disruption of the nanoscale membrane bridges inhibits the increase in CD276 and CD137 expression both in vitro and in vivo suggests that the nanoscale membrane bridge-mediated cancer cell–endothelial communication contribute to the process. The gene discussed is TNFRSF9; the disease is cancer.