@article{48b90cc3d04a4ac4aa23779ac85ea6d5,
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",
abstract = "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.",
keywords = "Behavior, Cancer, Fatigue, Indoleamine 2,3-dioxygenase, Mouse",
author = "Vichaya, {Elisabeth G.} and Vermeer, {Daniel W.} and David Budac and Anna Lee and Aaron Grossberg and Vermeer, {Paola D.} and Lee, {John H.} and Robert Dantzer",
note = "Funding Information: FuNDINg: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Cancer Institute of the National Institutes of Health (R01 CA193522, R.D.). Additional support came from the University of Texas MD Anderson Cancer Center and the National Institutes of Health MD Anderson Cancer Center Support Grant (P30 CA016672). The content is solely the responsibility of the authors and does not necessarily represent the official view of the funding sources. Funding Information: The authors thank Boehringer Ingelheim (Ingelheim, Germany) for providing the IDOInh. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Cancer Institute of the National Institutes of Health (R01 CA193522, R.D.). Additional support came from the University of Texas MD Anderson Cancer Center and the National Institutes of Health MD Anderson Cancer Center Support Grant (P30 CA016672). The content is solely the responsibility of the authors and does not necessarily represent the official view of the funding sources. Publisher Copyright: {\textcopyright} The Author(s) 2019.",
year = "2019",
month = aug,
day = "1",
doi = "10.1177/1178646919872508",
language = "English (US)",
volume = "12",
journal = "International Journal of Tryptophan Research",
issn = "1178-6469",
publisher = "Libertas Academica Ltd.",
}