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The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment.
Expert Opin Ther Targets. 2015 May; 19(5):605-15.EO

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+Show Affiliations

Medical University of Innsbruck, Biocenter, Division of Medical Biochemistry , Innsbruck 6020 , Austria.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

25684107

Citation

Gostner, Johanna M., et al. "The Potential of Targeting Indoleamine 2,3-dioxygenase for Cancer Treatment." Expert Opinion On Therapeutic Targets, vol. 19, no. 5, 2015, pp. 605-15.
Gostner JM, Becker K, Überall F, et al. The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment. Expert Opin Ther Targets. 2015;19(5):605-15.
Gostner, J. M., Becker, K., Überall, F., & Fuchs, D. (2015). The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment. Expert Opinion On Therapeutic Targets, 19(5), 605-15. https://doi.org/10.1517/14728222.2014.995092
Gostner JM, et al. The Potential of Targeting Indoleamine 2,3-dioxygenase for Cancer Treatment. Expert Opin Ther Targets. 2015;19(5):605-15. PubMed PMID: 25684107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment. AU - Gostner,Johanna M, AU - Becker,Kathrin, AU - Überall,Florian, AU - Fuchs,Dietmar, Y1 - 2015/02/15/ PY - 2015/2/17/entrez PY - 2015/2/17/pubmed PY - 2015/12/23/medline KW - GTP-cyclohydrolase KW - anti-inflammatory KW - antiproliferative KW - immunosuppressive KW - indoleamine 2,3-dioxygenase KW - kynurenine KW - neopterin KW - tolerance KW - tryptophan KW - tumor SP - 605 EP - 15 JF - Expert opinion on therapeutic targets JO - Expert Opin. Ther. Targets VL - 19 IS - 5 N2 - 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. SN - 1744-7631 UR - https://www.unboundmedicine.com/medline/citation/25684107/The_potential_of_targeting_indoleamine_23_dioxygenase_for_cancer_treatment_ L2 - http://www.tandfonline.com/doi/full/10.1517/14728222.2014.995092 DB - PRIME DP - Unbound Medicine ER -