Tumor High Endothelial Venules and Lymphocyte Trafficking

Abstract

Blood vessels and tumor angiogenesis are generally associated with tumor growth and poor clinical outcome of cancer patients. However, it has been recently discovered that some blood vessels present within the tumor microenvironment can be associated with a good prognosis by contributing to tumor suppression rather than tumor growth. These specialized blood vessels, designated high endothelial venules (HEVs), are normally found in lymph nodes where they mediate high levels of lymphocyte extravasation from the blood. A high density of tumor HEVs in human breast carcinomas and melanomas was associated with high levels of cytotoxic lymphocyte infiltration, indicating that HEVs may participate in the eradication of tumors by facilitating the access of “killer” lymphocytes into tumor tissues. A better understanding of the mechanisms regulating tumor HEVs could thus have an important impact for cancer therapy. Dendritic cells and the lymphotoxin pathway have been shown to be critical for maintenance of HEV differentiation in lymph nodes and may also regulate tumor HEVs. In this chapter, we will first describe the unique properties of lymph node HEVs and their role in lymphocyte trafficking. We will then review the phenotypic characteristics of tumor HEVs and their association with lymphocyte infiltration and favorable clinical outcome of cancer patients. Finally, we will discuss the promising potential of tumor HEVs for cancer therapy.