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.

Keywords:

• anti-inflammatory
• antiproliferative
• GTP-cyclohydrolase
• immunosuppressive
• indoleamine 2,3-dioxygenase
• kynurenine
• neopterin
• tolerance
• tryptophan
• tumor

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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