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Inhibitors of indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees?

Nature Reviews Cancer volume 9, pages 445–452 (2009)Cite this article

Abstract

Indoleamine-2,3-dioxygenase (IDO) is an immunosuppressive enzyme capable of inhibiting a destructive maternal T cell response against allogeneic fetuses. Expression of IDO is evident in tumours and is thought to enable escape from immunologically mediated rejection. Consequently, clinical trials using an inhibitor of IDO, 1-methyltryptophan (1MT), have been initiated. However, a review of the current literature indicates that we are far from understanding the biological relevance of IDO expression during tumorigenesis. A better understanding of IDO biology is needed to comprehend the effect of IDO inhibitors and to provide a rationale for their therapeutic application in cancer.

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Figure 1: Indoleamine-2,3-dioxygenase (IDO)-induced tryptophan catabolism along the kynurenine pathway.
Figure 2: Modulation of immune responses by indoleamine-2,3-dioxygenase (IDO)-expressing cells.

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Acknowledgements

The authors thank K. Dennehy for substantial help with editing the manuscript. S.L. was supported by a Fortüne grant of from the University of Tübingen, Tübingen, Germany (1767-0-0).

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  1. stefan.loeb@med.uni-tuebingen.de

  2. peter.terness@med.uni-heidelberg.de

Authors and Affiliations

  1. Stefan Löb and Alfred Königsrainer are at the Department of General, Visceral and Transplant Surgery, University Hospital of Tubingen, Hoppe-Seyler-Strasse 3, 72076 Tubingen, Germany.,

    Stefan Löb & Alfred Königsrainer

  2. Department of Immunology, Hans-Georg Rammensee is at the Institute of Cell Biology, University of Tubingen, Auf der Morgenstelle 15, 72076 Tubingen, Germany.,

    Hans-Georg Rammensee

  3. Department of Transplantation Immunology, Gerhard Opelz and Peter Terness are at the Institute of Immunology, University of Heidelberg, INF-305, 69120 Heidelberg, Germany.,

    Gerhard Opelz & Peter Terness

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Löb, S., Königsrainer, A., Rammensee, HG. et al. Inhibitors of indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees?. Nat Rev Cancer 9, 445–452 (2009). https://doi.org/10.1038/nrc2639

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