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Inhibition of Indoleamine 2,3 Dioxygenase Does Not Improve Cancer-Related Symptoms in a Murine Model of Human Papilloma Virus–Related Head and Neck Cancer

The expression of indoleamine 2,3 dioxygenase (IDO) by tumors can contribute to immunotolerance, and IDO induced by inflammation can also increase risk for the development of behavioral alterations. Thus, this study was initiated to determine whether IDO inhibition, intended to facilitate tumor clea...

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Autores principales: Vichaya, Elisabeth G, Vermeer, Daniel W, Budac, David, Lee, Anna, Grossberg, Aaron, Vermeer, Paola D, Lee, John H, Dantzer, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716175/
https://www.ncbi.nlm.nih.gov/pubmed/31496720
http://dx.doi.org/10.1177/1178646919872508
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author Vichaya, Elisabeth G
Vermeer, Daniel W
Budac, David
Lee, Anna
Grossberg, Aaron
Vermeer, Paola D
Lee, John H
Dantzer, Robert
author_facet Vichaya, Elisabeth G
Vermeer, Daniel W
Budac, David
Lee, Anna
Grossberg, Aaron
Vermeer, Paola D
Lee, John H
Dantzer, Robert
author_sort Vichaya, Elisabeth G
collection PubMed
description The expression of indoleamine 2,3 dioxygenase (IDO) by tumors can contribute to immunotolerance, and IDO induced by inflammation can also increase risk for the development of behavioral alterations. Thus, this study was initiated to determine whether IDO inhibition, intended to facilitate tumor clearance in response to treatment, attenuates behavioral alterations associated with tumor growth and treatment. We used a murine model of human papilloma virus–related head and neck cancer. We confirmed that tumor cells express IDO and expression was increased by radiotherapy. Interestingly, inhibition of IDO activation by the competitive inhibitor 1-methyl tryptophan mildly exacerbated treatment-associated burrowing deficits (burrowing is a sensitive index of sickness in tumor-bearing mice). Genetic deletion of IDO worsened tumor outcomes and had no effect on the behavioral response as by decreased burrowing or reduced voluntary wheel running. In contrast, oral administration of a specific inhibitor of IDO1 provided no apparent benefit on the tumor response to cancer therapy, yet decreased voluntary wheel-running activity independent of treatment. These results indicate that, independent of its potential effect on tumor clearance, inhibition of IDO does not improve cancer-related symptoms.
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spelling pubmed-67161752019-09-06 Inhibition of Indoleamine 2,3 Dioxygenase Does Not Improve Cancer-Related Symptoms in a Murine Model of Human Papilloma Virus–Related Head and Neck Cancer Vichaya, Elisabeth G Vermeer, Daniel W Budac, David Lee, Anna Grossberg, Aaron Vermeer, Paola D Lee, John H Dantzer, Robert Int J Tryptophan Res Original Research The expression of indoleamine 2,3 dioxygenase (IDO) by tumors can contribute to immunotolerance, and IDO induced by inflammation can also increase risk for the development of behavioral alterations. Thus, this study was initiated to determine whether IDO inhibition, intended to facilitate tumor clearance in response to treatment, attenuates behavioral alterations associated with tumor growth and treatment. We used a murine model of human papilloma virus–related head and neck cancer. We confirmed that tumor cells express IDO and expression was increased by radiotherapy. Interestingly, inhibition of IDO activation by the competitive inhibitor 1-methyl tryptophan mildly exacerbated treatment-associated burrowing deficits (burrowing is a sensitive index of sickness in tumor-bearing mice). Genetic deletion of IDO worsened tumor outcomes and had no effect on the behavioral response as by decreased burrowing or reduced voluntary wheel running. In contrast, oral administration of a specific inhibitor of IDO1 provided no apparent benefit on the tumor response to cancer therapy, yet decreased voluntary wheel-running activity independent of treatment. These results indicate that, independent of its potential effect on tumor clearance, inhibition of IDO does not improve cancer-related symptoms. SAGE Publications 2019-08-28 /pmc/articles/PMC6716175/ /pubmed/31496720 http://dx.doi.org/10.1177/1178646919872508 Text en © The Author(s) 2019 http://www.creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research
Vichaya, Elisabeth G
Vermeer, Daniel W
Budac, David
Lee, Anna
Grossberg, Aaron
Vermeer, Paola D
Lee, John H
Dantzer, Robert
Inhibition of Indoleamine 2,3 Dioxygenase Does Not Improve Cancer-Related Symptoms in a Murine Model of Human Papilloma Virus–Related Head and Neck Cancer
title Inhibition of Indoleamine 2,3 Dioxygenase Does Not Improve Cancer-Related Symptoms in a Murine Model of Human Papilloma Virus–Related Head and Neck Cancer
title_full Inhibition of Indoleamine 2,3 Dioxygenase Does Not Improve Cancer-Related Symptoms in a Murine Model of Human Papilloma Virus–Related Head and Neck Cancer
title_fullStr Inhibition of Indoleamine 2,3 Dioxygenase Does Not Improve Cancer-Related Symptoms in a Murine Model of Human Papilloma Virus–Related Head and Neck Cancer
title_full_unstemmed Inhibition of Indoleamine 2,3 Dioxygenase Does Not Improve Cancer-Related Symptoms in a Murine Model of Human Papilloma Virus–Related Head and Neck Cancer
title_short Inhibition of Indoleamine 2,3 Dioxygenase Does Not Improve Cancer-Related Symptoms in a Murine Model of Human Papilloma Virus–Related Head and Neck Cancer
title_sort inhibition of indoleamine 2,3 dioxygenase does not improve cancer-related symptoms in a murine model of human papilloma virus–related head and neck cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6716175/
https://www.ncbi.nlm.nih.gov/pubmed/31496720
http://dx.doi.org/10.1177/1178646919872508
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