Abstract
The enzyme indoleamine 2,3-dioxygenase (IDO) regulates immune responses through the capacity to degrade the essential amino acid tryptophan into kynurenine and other downstream metabolites that suppress effector T-cell function and favour the differentiation of regulatory T cells. Considerable experimental evidence indicates that IDO can be expressed by dendritic cells, by tumour cells or by surrounding stromal cells, either within proximity of the tumour or at distal sites. Recent advances in the biochemistry of IDO and in our understanding of the biological relevance of IDOmediated tryptophan consumption to the establishment of dominant immune tolerance to cancer will be summarised and discussed. Within the wider context of cancer immunotherapy, this Review also delineates how IDO could be exploited as a molecular target for therapeutic intervention in order to boost anti-cancer immunity.
Keywords: Indoleamine 2,3-dioxygenase, immune tolerance, regulatory T cell, haematopoietic growth factors, cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets
Title: Targeting Indoleamine 2,3-dioxygenase (IDO) to Counteract Tumour- Induced ImmuneDysfunction: From Biochemistry to Clinical Development
Volume: 9 Issue: 2
Author(s): S. Rutella, G. Bonanno and R. De Cristofaro
Affiliation:
Keywords: Indoleamine 2,3-dioxygenase, immune tolerance, regulatory T cell, haematopoietic growth factors, cancer
Abstract: The enzyme indoleamine 2,3-dioxygenase (IDO) regulates immune responses through the capacity to degrade the essential amino acid tryptophan into kynurenine and other downstream metabolites that suppress effector T-cell function and favour the differentiation of regulatory T cells. Considerable experimental evidence indicates that IDO can be expressed by dendritic cells, by tumour cells or by surrounding stromal cells, either within proximity of the tumour or at distal sites. Recent advances in the biochemistry of IDO and in our understanding of the biological relevance of IDOmediated tryptophan consumption to the establishment of dominant immune tolerance to cancer will be summarised and discussed. Within the wider context of cancer immunotherapy, this Review also delineates how IDO could be exploited as a molecular target for therapeutic intervention in order to boost anti-cancer immunity.
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Cite this article as:
Rutella S., Bonanno G. and De Cristofaro R., Targeting Indoleamine 2,3-dioxygenase (IDO) to Counteract Tumour- Induced ImmuneDysfunction: From Biochemistry to Clinical Development, Endocrine, Metabolic & Immune Disorders - Drug Targets 2009; 9 (2) . https://dx.doi.org/10.2174/187153009788452453
DOI https://dx.doi.org/10.2174/187153009788452453 |
Print ISSN 1871-5303 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3873 |
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