Article: article from journal or magazin.
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Endothelin B receptor, a new target in cancer immune therapy.
Clinical Cancer Research
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; ReviewPublication Status: ppublish
The endothelins and their G protein-coupled receptors A and B have been implicated in numerous diseases and have recently emerged as pivotal players in a variety of malignancies. Tumors overexpress the endothelin 1 (ET-1) ligand and the endothelin-A-receptor (ET(A)R). Their interaction induces tumor growth and metastasis by promoting tumor cell survival and proliferation, angiogenesis, and tissue remodeling. On the basis of results from xenograft models, drug development efforts have focused on antagonizing the autocrine-paracrine effects mediated by ET-1/ET(A)R. In this review, we discuss a novel role of the endothelin-B-receptor (ET(B)R) in tumorigenesis and the effect of its blockade during cancer immune therapy. We highlight key characteristics of the B receptor such as its specific overexpression in the tumor compartment; and specifically, in the tumor endothelium, where its activation by ET-1 suppresses T-cell adhesion and homing to tumors. We also review our recent findings on the effects of ET(B)R-specific blockade in increasing T-cell homing to tumors and enhancing the efficacy of otherwise ineffective immunotherapy.
Animals, Endothelium, Vascular/drug effects, Endothelium, Vascular/metabolism, Humans, Immunotherapy/methods, Intercellular Adhesion Molecule-1/metabolism, Models, Biological, Neoplasms/immunology, Neoplasms/metabolism, Oligopeptides/pharmacology, Piperidines/pharmacology, Receptor, Endothelin B/antagonists & inhibitors, Receptor, Endothelin B/metabolism, T-Lymphocytes/drug effects, T-Lymphocytes/immunology
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