Proceedings of the National Academy of Sciences· 2012Q1
Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase
- 570citations
- Q1SCImago
- 2012year
Short summary
Inhibition of the hepatic enzyme tryptophan 2,3-dioxygenase (TDO) restores the ability of mice to reject TDO-expressing tumors, establishing a new mechanism of tumoral immune resistance and a potential therapeutic target.
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Key points
- Enzymatically active TDO is expressed in a significant proportion of human tumors.
- Tumoral TDO expression prevents rejection of tumors by immunized mice in a preclinical model.
- A developed TDO inhibitor restored tumor rejection in mice when administered systemically.
- TDO inhibition represents a novel mechanism to overcome tumoral immune resistance.
AI-generated from the title and abstract; the full text is not read.
Abstract
Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO1) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance, and IDO1 inhibition is an active area of drug development. Tryptophan 2,3-dioxygenase (TDO) is an unrelated hepatic enzyme that also degrades tryptophan along the kynurenine pathway. Here, we show that enzymatically active TDO is expressed in a significant proportion of human tumors. In a preclinical model, TDO expression by tumors prevented their rejection by immunized mice. We developed a TDO inhibitor, which, upon systemic treatment, restored the ability of mice to reject TDO-expressing tumors. Our results describe a mechanism of tumoral immune resistance based on TDO expression and establish proof-of-concept for the use of TDO inhibitors in cancer therapy.
The authors' abstract, as published at the source. Proceedings of the National Academy of Sciences, 2012 · DOI ↗
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Field: Biological Psychiatry
Biological PsychiatryNeuroscience