TY - JOUR
T1 - Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells
AU - Lob, Stefan
AU - Konigsrainer, Alfred
AU - Schafer, Richard
AU - Rammensee, Hans-Georg
AU - Opelz, Gerhard
AU - Terness, Peter
N1 - Löb: Department of General, Visceral and Transplant Surgery, University Hospital of Tubingen, Tubingen, Germany
PY - 2008/2/15
Y1 - 2008/2/15
N2 - 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.
AB - 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.
KW - Cytokines/pharmacology
KW - Dendritic Cells/drug effects
KW - Gene Expression Regulation, Enzymologic
KW - Humans
KW - Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics
KW - Kinetics
KW - RNA, Small Interfering/genetics
KW - Stereoisomerism
KW - Transfection
KW - Tryptophan/analogs & derivatives
U2 - 10.1182/blood-2007-10-116111
DO - 10.1182/blood-2007-10-116111
M3 - Original Article
C2 - 18045970
SN - 0006-4971
VL - 111
SP - 2152
EP - 2154
JO - BLOOD
JF - BLOOD
IS - 4
ER -