Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase.
T lymphocytes undergo proliferation arrest when exposed to tryptophan shortage, which can be provoked by indoleamine 2,3-dioxygenase (IDO), an enzyme that is expressed in placenta and catalyzes tryptophan degradation. Here we show that most human tumors constitutively express IDO. We also observed that expression of IDO by immunogenic mouse tumor cells prevents their rejection by preimmunized mice. This effect is accompanied by a lack of accumulation of specific T cells at the tumor site and can be partly reverted by systemic treatment of mice with an inhibitor of IDO, in the absence of noticeable toxicity. These results suggest that the efficacy of therapeutic vaccination of cancer patients might be improved by concomitant administration of an IDO inhibitor.
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019139:Tumor Escape
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; C020774:alpha-methyltryptophan; D014364:Tryptophan; D014366:Tryptophan Oxygenase