Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells

被引：149

作者：

Lob, Stefan ^{[2
,3
]}

Konigsrainer, Alfred ^{[2
]}

Schafer, Richard ^{[4
]}

Rammensee, Hans-Georg ^{[3
]}

Opelz, Gerhard ^{[1
]}

Terness, Peter ^{[1
]}

机构：

[1] Univ Heidelberg, Inst Immunol, Dept Transplantat Immunol, INF 305, D-69120 Heidelberg, Germany

[2] Univ Hosp, Dept Gen Visceral & Transplant Surg, Tubingen, Germany

[3] Univ Tubingen, Dept Immunol, Inst Cell Biol, Tubingen, Germany

[4] Univ Tubingen, Inst Clin & Expt Transfus Med, Tubingen, Germany

来源：

BLOOD | 2008年 / 111卷 / 04期

关键词：

DRAINING LYMPH-NODES; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN DEGRADATION; 1-METHYL-TRYPTOPHAN; RESPONSES;

D O I：

10.1182/blood-2007-10-116111

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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-methyltryptophan (D-1MT). Here we show that human dendritic cells (DCs) express both IDO-1 and IDO-2, but that only IDO-1 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.

引用

页码：2152 / 2154

页数：3

共 15 条

[1] 1-methyl-tryptophan can interfere with TLR signaling in dendritic cells independently of IDO activity [J].

Agaugue, Sophie ;

Perrin-Cocon, Laure ;

Coutant, Frederic ;

Andre, Patrice ;

Lotteau, Vincent .

JOURNAL OF IMMUNOLOGY, 2006, 177 (04) :2061-2071

[2] Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice [J].

Ball, Helen J. ;

Sanchez-Perez, Angeles ;

Weiser, Silvia ;

Austin, Christopher J. D. ;

Astelbauer, Florian ;

Miu, Jenny ;

McQuillan, James A. ;

Stocker, Roland ;

Jermiin, Lars S. ;

Hunt, Nicholas H. .

GENE, 2007, 396 (01) :203-213

[3] The hallmarks of cancer [J].

Hanahan, D ;

Weinberg, RA .

CELL, 2000, 100 (01) :57-70

[4] Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses [J].

Hou, De-Yan ;

Muller, Alexander J. ;

Sharma, Madhav D. ;

DuHadaway, James ;

Banerjee, Tinku ;

Johnson, Maribeth ;

Mellor, Andrew L. ;

Prendergasts, George C. ;

Munn, David H. .

CANCER RESEARCH, 2007, 67 (02) :792-801

[5] The role of L-tryptophan transport in L-tryptophan degradation by indoleamine 2,3-dioxygenase in human placental explants [J].

Kudo, Y ;

Boyd, CAR .

JOURNAL OF PHYSIOLOGY-LONDON, 2001, 531 (02) :417-423

[6] Are indoleamine-2,3-dioxygenase producing human dendritic cells a tool for suppression of allogeneic T-cell responses? [J].

Loeb, Stefan ;

Ebner, Susanne ;

Wagner, Silvia ;

Weinreich, Juergen ;

Schaefer, Richard ;

Koenigsrainer, Alfred .

TRANSPLANTATION, 2007, 83 (04) :468-473

[7] Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan [J].

Metz, Richard ;

DuHadaway, James B. ;

Kamasani, Uma ;

Laury-Kleintop, Lisa ;

Muller, Alexander J. ;

Prendergast, George C. .

CANCER RESEARCH, 2007, 67 (15) :7082-7087

[8] Indoleamine 2,3-dioxygenase and tumor-induced tolerance [J].

Munn, David H. ;

Mellor, Andrew L. .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (05) :1147-1154

[9] Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase [J].

Munn, DH ;

Sharma, MD ;

Lee, JR ;

Jhaver, KG ;

Johnson, TS ;

Keskin, DB ;

Marshall, B ;

Chandler, P ;

Antonia, SJ ;

Burgess, R ;

Slingluff, CL ;

Mellor, AL .

SCIENCE, 2002, 297 (5588) :1867-1870

[10] Prevention of allogeneic fetal rejection by tryptophan catabolism [J].

Munn, DH ;

Zhou, M ;

Attwood, JT ;

Bondarev, I ;

Conway, SJ ;

Marshall, B ;

Brown, C ;

Mellor, AL .

SCIENCE, 1998, 281 (5380) :1191-1193

← 1 2 →