title: The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment.
abstract: BACKGROUND
  Degradation of the essential amino acid tryptophan via indoleamine 2,3-dioxygenase (IDO1) represents an important antiproliferative strategy of the cellular immune response. Tryptophan shortage and accumulation of kynurenine downstream products also affect T-cell responses, providing a negative feedback control of immune activation. IDO1 activity can promote a regulatory phenotype in both T cells and dendritic cells. These phenomena can support tumor immune escape.
  
  
  METHODS
  IDO1 activity reflects the course of several malignancies, and determination of kynurenine to tryptophan ratio in serum/plasma can be used to assess immune activation. Moreover, the accelerated breakdown of tryptophan has been correlated with the development of cancer-associated disturbances such as anemia, weight loss and depression. Tumoral IDO1 expression was correlated with a poor prognosis in several types of tumors, which makes it to an interesting target for immunotherapy. In addition, according to recent data, a role of trytptophan 2,3-dioxygenase (TDO) in tumorigenesis cannot be excluded.
  
  
  CONCLUSIONS
  Tryptophan metabolism is critical for cell proliferation, inflammation and immunoregulation. Accelerated tryptophan breakdown favors tumor immune escape. Accordingly, targeting IDO1 by immunotherapy may represent a favorable approach; however, blocking crucial immunoregulatory pathways could also introduce the risk of immune system overactivation, finally leading to unresponsiveness.
authors: Medical University of Innsbruck, Biocenter, Division of Medical Biochemistry , Innsbruck 6020 , Austria.
authors: Johanna M
authors: JM
authors: Gostner
authors: Kathrin
authors: K
authors: Becker
authors: Florian
authors: F
authors: Überall
authors: Dietmar
authors: D
authors: Fuchs
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007737:Kynurenine / Q000097:blood / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014364:Tryptophan / Q000097:blood / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan
keywords: GTP-cyclohydrolase; anti-inflammatory; antiproliferative; immunosuppressive; indoleamine 2,3-dioxygenase; kynurenine; neopterin; tolerance; tryptophan; tumor