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Role of IDO in Dendritic Cell Differentiation and Function in Cancer

  • Alexey Popov
  • Joachim L. Schultze
Chapter

Abstract

Expression of tryptophan-catabolizing enzyme indoleamine-pyrrole 2,3-dioxygenase (IDO) has been associated with the regulatory phenotype of tumor-associated dendritic cells, along with other tolerogenic mechanisms, including production of immunomodulatory cytokines and expression of immune-inhibitory receptors. IDO activation in dendritic cells leads to tryptophan depletion and accumulation of its toxic downstream metabolites which in concert directly suppress proliferation of T cells and induce T-cell apoptosis. Furthermore, IDO-positive dendritic cells promote the induction of regulatory T cells, which further impair protective immunity against tumors. In the context of cancer, IDO induction in dendritic cells can be triggered by receptors expressed by regulatory T cells, such as CTLA4 and GITR, and by soluble tumor-associated factors, such as prostaglandin E2, in close alliance with TNF signaling. Immunosuppressive effects of enzymatically active IDO can be overcome by specific inhibitors such as 1-methyl-tryptophan which can be used for therapeutic purposes.

Keywords

Dendritic Cell Human Dendritic Cell Tryptophan Depletion Tryptophan Metabolite Murine Dendritic Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Laboratory for Genomics and Immunoregulation, Program Unit Molecular Immune & Cell BiologyLIMES (Life and Medical Sciences), University of BonnBonnGermany

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