Immunological Regulation of Vascular Inflammation During Cancer Metastasis

Metastasis is the predominant cause of cancer-related mortality, despite being a highly inefficient process overall. The vasculature is the gatekeeper for tumor cell seeding within the secondary tissue microenvironment-the rate limiting step of the metastatic cascade. Therefore, factors that regulate vascular physiology dramatically influence cancer outcomes. There are a myriad of physiologic circumstances that not only influence the intrinsic capacity of tumor cells to cross the endothelial barrier, but also that regulate vascular inflammation and barrier integrity to enable extravasation into the metastatic niche. These processes are highly dependent on inflammatory cues largely initiated by the innate immune compartment, that are meant to help re-establish tissue homeostasis, but instead become hijacked by cancer cells. Here, we discuss the scientific advances in understanding the interactions between innate immune cells and the endothelium, describe their influence on cancer metastasis, and evaluate potential therapeutic interventions for the alleviation of metastatic disease. By triangulating the relationship between immune cells, endothelial cells, and tumor cells, we will gain greater insight into how to impede the metastatic process by focusing on its most vulnerable phases, thereby reducing metastatic spread and cancer-related mortality.