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Is IDO a key enzyme bridging the gap between tumor escape and tolerance induction?

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Abstract

Background

Shaping immune responses to prevent tumor-induced tolerance or transplant rejection after solid organ transplantation is a permanently expanding field of research. Immunological tolerance, in this case, is a double-edged sword. Tumors escape immune surveillance by creating an abnormal state of tolerance towards their own antigens, whereas transplantation medicine is challenged to develop new strategies to induce allograft-specific immunological tolerance. One mechanism possibly capable of achieving immunoregulation is based on indoleamine-2,3-dioxygenase (IDO).

Objective

This overview article focuses on IDO-mediated tryptophan catabolism with special regard to its role in cancer and transplantation immunology.

Results

The historical view about IDO as a host’s antimicrobial defence mechanism has been extended by the observation that its expression is essential for successful allogeneic pregnancy. Subsequent studies analysing IDO as an immune-regulatory enzyme describe its implications in cancer immune escape, as chemical abrogation of enzyme activity with 1-methyl-tryptophan (1-MT), results in enhanced antitumor responses in animal models. Therefore, a clinical trial treating cancer patients with 1-MT has been started. IDO also seems to play an essential role in the control of allo- and autoreactive T cell responses. CTLA4-Ig is able to induce IDO expression in dendritic cells (DCs) and consequently renders them tolerogenic, which might provide one explanation for the observed therapeutic effects of abatacept and belatacept.

Conclusion

There is evidence that IDO achieves immune modulation in several animal models. However, in humans, this remains controversially discussed.

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Acknowledgments

The authors thank Lynne Yakes and Hans-Georg Rammensee for assistance in preparing the manuscript.

This work was supported by a Fortüne grant of the University of Tübingen (1636-0-0 to S.L.).

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  1. Department of General, Visceral and Transplantsurgery, Eberhard Karls University, Hoppe-Seyler-Straβe 3, 72076, Tübingen, Germany

    Stefan Löb & Alfred Königsrainer

  2. Department of Immunology, Interfacultary Institute of Cell Biology, Eberhard Karls University, Auf der Morgenstelle 15, 72076, Tübingen, Germany

    Stefan Löb

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Löb, S., Königsrainer, A. Is IDO a key enzyme bridging the gap between tumor escape and tolerance induction?. Langenbecks Arch Surg 393, 995–1003 (2008). https://doi.org/10.1007/s00423-007-0245-7

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