Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells

Blood. 2008 Feb 15;111(4):2152-4. doi: 10.1182/blood-2007-10-116111. Epub 2007 Nov 28.

Abstract

Clinical trials have been started with the aim of inducing tumor immunity by blocking the immunosuppressive action of indoleamine-2,3-dioxygenase (IDO) with the IDO2-inhibitor dextro-1-methyl-tryptophan (D-1MT). Here we show that human dendritic cells (DCs) express both IDO-1 and IDO-2, but that only IDO1 mediates tryptophan catabolism; furthermore, its activity is blocked by levo-1MT, whereas D-1MT is inefficient. Consequently, in humans any possible antitumor effects of D-1MT cannot be attributed to abrogation of IDO activity in DCs as described in this study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / pharmacology
  • Dendritic Cells / drug effects
  • Dendritic Cells / enzymology*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Kinetics
  • RNA, Small Interfering / genetics
  • Stereoisomerism
  • Transfection
  • Tryptophan / analogs & derivatives*
  • Tryptophan / pharmacology

Substances

  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • RNA, Small Interfering
  • Tryptophan
  • 1-methyltryptophan