Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells.
Clinical trials have been started with the aim of inducing tumor immunity by blocking the immunosuppressive action of indoleamine-2,3-dioxygenase (IDO) with the IDO2-inhibitor dextro-1-methyl-tryptophan (D-1MT). Here we show that human dendritic cells (DCs) express both IDO-1 and IDO-2, but that only IDO1 mediates tryptophan catabolism; furthermore, its activity is blocked by levo-1MT, whereas D-1MT is inefficient. Consequently, in humans any possible antitumor effects of D-1MT cannot be attributed to abrogation of IDO activity in DCs as described in this study.
Department of General, Visceral and Transplant Surgery, University Hospital of Tubingen, Tubingen, Germany.
Stefan
S
Lob
Alfred
A
Konigsrainer
Richard
R
Schafer
Hans-Georg
HG
Rammensee
Gerhard
G
Opelz
Peter
P
Terness
D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D034741:RNA, Small Interfering / Q000235:genetics; D013237:Stereoisomerism; D014162:Transfection; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D034741:RNA, Small Interfering; D014364:Tryptophan; C525396:1-methyltryptophan