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Open Access 01-08-2012 | Focussed Research Review

The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase

Author: Mads Hald Andersen

Published in: Cancer Immunology, Immunotherapy | Issue 8/2012

Abstract

Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in many settings including cancer. In recent years, we have described spontaneous CD8⁺ as well as CD4⁺ T-cell reactivity against IDO in the tumor microenvironment of different cancer patients as well as in the peripheral blood of both cancer patients and to a lesser extent in healthy donors. We have demonstrated that IDO-reactive CD8⁺ T cells were peptide-specific, cytotoxic effector cells, which are able to recognize and kill IDO-expressing cells including tumor cells as well as dendritic cells. Consequently, IDO may serve as a widely applicable target for immunotherapeutic strategies with a completely different function as well as expression pattern compared to previously described antigens. IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, and IDO-based immunotherapy may consequently be synergistic with additional immunotherapy. In this regard, we have shown that the presence of IDO-specific T cells boosted immunity against CMV and tumor antigens by eliminating IDO⁺ suppressive cells and changing the regulatory microenvironment. The current review summarizes current knowledge of IDO as a T-cell antigen, reports the initial results that are suggesting a general function of IDO-specific T cells in immunoregulation, and discusses future opportunities.

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Title: The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase
Author: Mads Hald Andersen
Publication date: 01-08-2012
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 8/2012
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-012-1234-4

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