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Erschienen in:

01.07.2015 | Editors' Invited Manuscript

The role of IDO in brain tumor immunotherapy

verfasst von: Lijie Zhai, Kristen L. Lauing, Alan L. Chang, Mahua Dey, Jun Qian, Yu Cheng, Maciej S. Lesniak, Derek A. Wainwright

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2015

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Abstract

Malignant glioma comprises the majority of primary brain tumors. Coincidently, most of those malignancies express an inducible tryptophan catabolic enzyme, indoleamine 2,3 dioxygenase 1 (IDO1). While IDO1 is not normally expressed at appreciable levels in the adult central nervous system, it’s rapidly induced and/or upregulated upon inflammatory stimulus. The primary function of IDO1 is associated with conversion of the essential amino acid, tryptophan, into downstream catabolites known as kynurenines. The depletion of tryptophan and/or accumulation of kynurenine has been shown to induce T cell deactivation, apoptosis and/or the induction of immunosuppressive programming via the expression of FoxP3. This understanding has informed immunotherapeutic design for the strategic development of targeted molecular therapeutics that inhibit IDO1 activity. Here, we review the current knowledge of IDO1 in brain tumors, pre-clinical studies targeting this enzymatic pathway, alternative tryptophan catabolic mediators that compensate for IDO1 loss and/or inhibition, as well as proposed clinical strategies and questions that are critical to address for increasing future immunotherapeutic effectiveness in patients with incurable brain cancer.

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Titel: The role of IDO in brain tumor immunotherapy
verfasst von: Lijie Zhai
Kristen L. Lauing
Alan L. Chang
Mahua Dey
Jun Qian
Yu Cheng
Maciej S. Lesniak
Derek A. Wainwright
Publikationsdatum: 01.07.2015
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2015
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-014-1687-8

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