Indoleamine 2,3 Dioxygenase Is It an Immune Suppressor英文文献.pdfVIP

REVIEW ARTICLE Indoleamine 2,3-Dioxygenase Is It an Immune Suppressor? Hatem Soliman, MD, Melanie Mediavilla-Varela, PhD, and Scott Antonia, MD, PhD has garnered a significant amount of attention is an enzyme involved Abstract: This article covers what is currently known about the role of the in the metabolism of the essential amino acid tryptophan called enzyme indoleamine 2,3-dioxygenase (IDO) in cancer-related immunosup- indoleamine 2,3-dioxygenase (IDO, EC 2). This article pression and the clinical research on IDO inhibitors. A PUBMED search was will summarize the pertinent data surrounding its role in cancer performed using the terms IDO, indoleamine 2,3-dioxygenase, 1-MT. IDO is immunotherapy. an inducible enzyme that catalyzes the rate-limiting first step in tryptophan catabolism. This enzyme is overexpressed in response to IFN in a variety of BACKGROUND different malignancies. IDO causes immunosuppression through breakdown of tryptophan in the tumor microenvironment and tumor-draining lymph Kotake and Masayama described an enzyme called trypto- nodes. The depletion of tryptophan and toxic catabolites renders effector T phan oxygenase constitutively expressed in the liver of mammals in cells inactive and dendritic cells immunosuppressive. Preclinical data sug- 1936, and this enzyme was initially thought to be the sole enzyme gest that IDO inhibition can delay