Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 2497-2502 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 109 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 14 Feb 2012 |
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Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. / Pilotte, L.; Larrieu, P.; Stroobant, V.; Colau, D.; Dolušić, E.; Frédérick, R.; De Plaen, E.; Uyttenhove, C.; Wouters, J.; Masereel, B.; Van Den Eynde, B.J.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 7, 14.02.2012, p. 2497-2502.Research output: Contribution to journal › Article
TY - JOUR
T1 - Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase
AU - Pilotte, L.
AU - Larrieu, P.
AU - Stroobant, V.
AU - Colau, D.
AU - Dolušić, E.
AU - Frédérick, R.
AU - De Plaen, E.
AU - Uyttenhove, C.
AU - Wouters, J.
AU - Masereel, B.
AU - Van Den Eynde, B.J.
PY - 2012/2/14
Y1 - 2012/2/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84857136779&partnerID=8YFLogxK
U2 - 10.1073/pnas.1113873109
DO - 10.1073/pnas.1113873109
M3 - Article
VL - 109
SP - 2497
EP - 2502
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 7
ER -