The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment.

Abstract

INTRODUCTION:

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.

AREAS COVERED:

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.

EXPERT OPINION:

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: Johanna M Gostner, Kathrin Becker, Florian Überall, Dietmar Fuchs
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 19 Issue 5 Pg. 605-15 (May 2015) ISSN: 1744-7631 [Electronic] England
• PMID: 25684107 (Publication Type: Journal Article, Review)

Chemical References

• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Kynurenine
• Tryptophan

Topics

• Animals
• Cell Proliferation
• Dendritic Cells (immunology)
• Humans
• Immunity, Cellular
• Immunotherapy (methods)
• Indoleamine-Pyrrole 2,3,-Dioxygenase (immunology)
• Inflammation (immunology)
• Kynurenine (blood, metabolism)
• Neoplasms (immunology, therapy)
• T-Lymphocytes (immunology)
• Tryptophan (blood, metabolism)