Indoleamine 2,3-dioxygenase and tumor-induced tolerance

Munn, David H.
Mellor, Andrew L.

¹Department of Pediatrics, Medical College of Georgia, Augusta, Georgia, USA.
²Department of Medicine, Medical College of Georgia, Augusta, Georgia, USA.

Address correspondence to: David H. Munn, Immunotherapy Program, MCG Cancer Center, Room CN-4141, Augusta, Georgia 30912, USA. Phone: (706) 721-7141; Fax: (706) 721-8732; E-mail: [email protected].

Nonstandard abbreviations used: CpG ODN, oligodeoxynucleotide(s) containing one or more unmethylated CpG dinucleotides; CTLA4, cytotoxic T lymphocyte–associated antigen 4; GCN2, general control nonderepressible 2; IDO, indoleamine 2,3-dioxygenase; 1MT, 1-methyl-tryptophan.

Conflict of interest: D.H. Munn and A.L. Mellor hold intellectual property interests in the use of IDO and IDO inhibitors and receive income, equity ownership, and research support from NewLink Genetics.

Citation for this article:J. Clin. Invest.117:1147–1154 (2007). doi:10.1172/JCI31178.

Journal of Clinical Investigation 117(5):p 1147-1154, May 2007.

Tumors arise from normal cells of the body through genetic mutation. Although such genetic mutation often leads to the expression of abnormal antigens, the immune system fails to respond effectively to these antigens; that is, it is tolerant of these antigens. This acquired state of tolerance must be overcome for cancer immunotherapy to succeed. Indoleamine 2,3-dioxygenase (IDO) is one molecular mechanism that contributes to tumor-induced tolerance. IDO helps create a tolerogenic milieu in the tumor and the tumor-draining lymph nodes, both by direct suppression of T cells and enhancement of local Treg-mediated immunosuppression. It can also function as an antagonist to other activators of antitumor immunity. Therefore, strategies to block IDO might enhance the effectiveness of tumor immunotherapy.