90. Can indoleamine 2,3-dioxygenase (IDO) be targeted to improve tumor clearance as well as attenuate cancer-related symptoms?

• Published in: Brain, behavior, and immunity behavior, and immunity, 2014-09, Vol.40, p.e26-e26
• Main Authors: Vichaya, E.G, Vermeer, D.W, Kavelaars, A, Lee, J.H, Dantzer, R
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2014.06.110

The tryptophan degrading enzyme IDO is expressed by tumor cells and immune cells in the tumor microenvironment. This creates a tolerogenic milieu that compromises tumor clearance. Further, IDO has been shown to be involved in cancer-related fatigue and inflammation-associated depression. As many cancer patients suffer from these symptoms, we sought to determine if inhibiting IDO using 1-methyl- l -tryptophan (1-MT) could improve tumor clearance and attenuate symptoms. C57BL/6J mice were injected with 1 × 106 tumor cells into the right hind leg to model HPV + head and neck cancer and 7 days later treated with 20 mg/m2 cisplatin and 8 Gy irradiation once weekly for three weeks. Half of the mice were provided 1-MT treated drinking water (5 mg/ml) beginning 2 days prior to tumor cell injection. 1-MT treatment decreased IDO activity as measured by the serum kynurenine/tryptophan ratio, and this was associated with decreased tumor growth and a trend toward improved survival. In a follow up study, burrowing (a sensitive behavioral measure of sickness) was measured before and after implantation of the tumor and during chemoradiation. Burrowing decreased over time and this effect was more pronounced in 1-MT treated mice. This data suggests that although targeting IDO may improve tumor clearance, it might also exacerbate cancer-related symptoms probably as a consequence of immune reactivation. A follow up study is currently underway to confirm these findings.