Role of IDO in Dendritic Cell Differentiation and Function in Cancer

  • Alexey Popov
  • Joachim L. Schultze


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.


Dendritic Cell Human Dendritic Cell Tryptophan Depletion Tryptophan Metabolite Murine Dendritic Cell 
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© 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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