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Dendritic Cells in Cancer pp 219–229Cite as

Role of IDO in Dendritic Cell Differentiation and Function in Cancer

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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.

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  1. Laboratory for Genomics and Immunoregulation, Program Unit Molecular Immune & Cell Biology, LIMES (Life and Medical Sciences), University of Bonn, Karlrobert-Kreiten Street 13, 53115, Bonn, Germany

    Alexey Popov

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  1. Alexey Popov
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  2. Joachim L. Schultze
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Correspondence to Alexey Popov .

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    Popov, A., Schultze, J.L. (2009). Role of IDO in Dendritic Cell Differentiation and Function in Cancer. In: Salter, R., Shurin, M. (eds) Dendritic Cells in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-88611-4_15

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