Indoleamine 2,3‐dioxygenase in T‐cell tolerance and tumoral immune escape

Immunological Reviews - Tập 222 Số 1 - Trang 206-221 - 2008
Jessica Katz1,2, Alexander J. Muller3,2, George C. Prendergast3,2,4
1Department of Medicine, Division of Hematology/Oncology, Lankenau Hospital, Wynnewood, PA, USA.
2Lankenau Institute for Medical Research, Wynnewood PA, USA
3Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
4Pathology, Anatomy, and Cell Biology, Jefferson Medical School, Thomas Jefferson University, Philadelphia, PA, USA.

Tóm tắt

Summary: Indoleamine 2, 3‐dioxygenase (IDO) degrades the essential amino acid tryptophan in mammals, catalyzing the initial and rate‐limiting step in the de novo biosynthesis nicotinamide adenine dinucleotide (NAD). Broad evidence implicates IDO and the tryptophan catabolic pathway in generation of immune tolerance to foreign antigens in tissue microenvironments. In particular, recent findings have established that IDO is overexpressed in both tumor cells and antigen‐presenting cells in tumor‐draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the normal physiologic state, IDO is important in creating an environment that limits damage to tissues due to an overactive immune system. However, by fostering immune suppression, IDO can facilitate the survival and growth of tumor cells expressing unique antigens that would be recognized normally as foreign. In preclinical studies, small‐molecule inhibitors of IDO can reverse this mechanism of immunosuppression, complementing classical cytotoxic cancer chemotherapeutic agents' ability to trigger regression of treatment‐resistant tumors. These results have encouraged the clinical translation of IDO inhibitors, the first of which entered phase I clinical trials in the fall of 2007. In this article, we survey the work defining IDO as an important mediator of peripheral tolerance, review evidence of IDO dysregulation in cancer cells, and provide an overview of the development of IDO inhibitors as a new immunoregulatory treatment modality for clinical trials.

Từ khóa


Tài liệu tham khảo

Burnet M., 1957, Cancer, a biologic approach, 1, 841

10.1038/nri1961

10.1016/j.immuni.2004.07.017

10.1158/0008-5472.CAN-05-4603

10.1056/NEJM200302063480620

10.1002/1097-0142(197107)28:1<89::AID-CNCR2820280117>3.0.CO;2-Q

Gutierrez‐Dalmau A, 2007, Immunosuppressive therapy and malignancy in organ transplant recipients, a systematic review, 67, 1167

10.1016/S0041-1345(98)01987-3

10.1006/gyno.2000.5942

Penn I., 2000, Post‐transplant malignancy, the role of immunosuppression, 23, 101

10.1053/rr.2000.5269

Penn I., 1998, Occurrence of cancers in immunosuppressed organ transplant recipients, Clin Transpl, 147

10.1097/00007890-199709150-00001

Penn I., 1997, Skin disorders in organ transplant recipients. External anogenital lesions, Arch Dermatol, 133, 221, 10.1001/archderm.1997.03890380093014

10.1038/nrc1586

10.1016/j.ccr.2005.02.013

10.1158/0008-5472.CAN-05-4128

10.1038/nrc1929

10.1126/science.281.5380.1191

Thomas SM, 1993, IFN‐gamma‐mediated antimicrobial response. Indoleamine 2,3‐dioxygenase‐deficient mutant host cells no longer inhibit intracellular Chlamydia spp. or Toxoplasma growth, J Immunol, 150, 5529, 10.4049/jimmunol.150.12.5529

Fujigaki S, 2002, l‐tryptophan‐l‐kynurenine pathway metabolism accelerated by Toxoplasma gondii infection is abolished in gamma interferon‐gene‐deficient mice, cross-regulation between inducible nitric oxide synthase and indoleamine-2,3-dioxygenase, 70, 779

10.1016/j.ijpara.2004.07.008

10.1128/JVI.02248-06

Boyland E, 1955, The estimation of tryptophan metabolites in the urine of patients with cancer of the bladder, Process Biochem, 60, v

Ambanelli U, 1962, Some aspects of tryptophan–nicotinic acid chain in Hodgkin's disease. Relative roles of tryptophan loading and vitamin supplementation on urinary excretion of metabolites, Haematol Lat, 5, 49

Ivanova VD., 1964, Disorders of Tryptophan Metabolism in Leukaemia, Acta Unio Int Contra Cancrum, 20, 1085

10.1016/S0140-6736(67)91301-3

10.1016/S0022-5347(17)62566-7

Hayaishi O, 1984, Progress in Tryptophan and Seratonin Research, 33

10.1016/0003-9861(67)90256-1

Higuchi K, 1963, Enzymatic formation of D‐kynurenine, Federation Proc, 22, 243

10.1016/S0021-9258(17)30447-7

10.1096/fasebj.5.11.1907934

10.1177/29.5.6788834

Sugimoto H, 2006, Crystal structure of human indoleamine 2,3‐dioxygenase, catalytic mechanism of O2 incorporation by a heme-containing dioxygenase, 103, 2611

10.1021/bi00439a013

10.1016/0006-291X(92)91590-M

10.1159/000133584

ArefayeneM et al. Identification of functional genetic variants of the indoleamine 2 3 dioxygenase gene. American Association for Cancer Research 97th Annual Meeting Proceedings; 2006 Apr 1–5 Washington DC: 1119.

10.1158/1078-0432.CCR-04-2671

Brandacher G, 2006, Prognostic value of indoleamine 2,3‐dioxygenase expression in colorectal cancer, effect on tumor-infiltrating T cells, 12, 1144

10.1016/j.clim.2004.05.004

10.1111/j.1349-7006.2007.00470.x

10.1593/neo.04658

10.1097/01.LAB.0000090158.68852.D1

10.1172/JCI21583

10.1158/1078-0432.CCR-04-1869

10.1158/1078-0432.CCR-05-1886

10.1111/j.1440-1746.2003.03259.x

10.1016/j.gene.2007.04.010

10.2174/138920007780362509

10.1158/0008-5472.CAN-07-1872

Muller AJ, 2008, Differential targeting of tryptophan catabolism in tumors and in tumor‐draining lymph nodes by stereoisomers of the IDO inhibitor 1‐methyl‐tryptophan, Int Congr Ser, 1304, 250, 10.1016/j.ics.2007.07.042

10.1016/j.immuni.2005.03.013

Yasui H, 1986, Interferon enhances tryptophan metabolism by inducing pulmonary indoleamine 2,3‐dioxygenase, its possible occurence in cancer patients, 83, 6622

Ozaki Y, 2008, Induction of indoleamine 2,3‐dioxygenase, a mechanism of the anti-tumor activity of interferon gamma, 85, 1242

Mellor AL, 1999, Tryptophan catabolism and T‐cell tolerance, immunosuppression by starvation?, 20, 469

10.1084/jem.189.9.1363

Grohmann U, 2003, Tolerance, DCs and tryptophan, much ado about IDO, 24, 242

10.1016/j.molmed.2003.11.003

10.1126/science.1117634

10.4049/jimmunol.177.11.8226

Mellor AL, 2004, IDO expression by dendritic cells, tolerance and trytophan catabolism, 4, 762

10.4049/jimmunol.139.7.2414

10.1002/jlb.45.1.29

10.4049/jimmunol.164.7.3596

10.1007/978-1-4615-4709-9_68

10.1089/107999000312531

10.1074/jbc.271.29.17247

10.1089/jir.1995.15.517

10.1074/jbc.271.32.19140

10.1089/jir.2005.25.20

10.1093/nar/25.21.4346

10.1182/blood-2005-03-0979

Wobser M, 2007, Dendritic cell based anti‐tumor vaccination, impact of functional indoleamine 2,3-dioxygenase expression, 56, 1017

10.1073/pnas.78.12.7327

10.1186/1471-2091-2-5

10.1189/jlb.0502220

Alberati‐Giani D, 1997, Differential regulation of indoleamine 2,3‐dioxygenase expression by nitric oxide and inflammatory mediators in IFN‐gamma‐activated murine macrophages and microglial cells, J Immunol, 159, 419, 10.4049/jimmunol.159.1.419

Daubener W, 1999, Inducible anti‐parasitic effector mechanisms in human uroepithelial cells, tryptophan degradation vs. NO production, 187, 143

10.1016/S0021-9258(17)36645-0

Hucke C, 2004, Nitric oxide‐mediated regulation of gamma interferon‐induced bacteriostasis, inhibition and degradation of human indoleamine 2,3-dioxygenase, 72, 2723

10.1021/bi060143j

10.1084/jem.20040942

Toker A, 2006, Akt signaling and cancer, surviving but not moving on, 66, 3963

Yuan W, 1998, Modulation of cellular tryptophan metabolism in human fibroblasts by transforming growth factor‐beta, selective inhibition of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA synthetase gene expression, 177, 174

10.1016/S1074-7613(03)00182-1

10.1084/jem.20050463

10.1158/0008-5472.CAN-04-3957

10.1016/S1074-7613(00)80195-8

10.1038/ni939

10.4049/jimmunol.173.8.5028

10.1084/jem.20041201

10.4049/jimmunol.171.4.1652

10.1093/intimm/dxh140

10.1038/ni1003

10.1038/ni846

10.1126/science.1073514

10.1038/nri1032

Piccirillo CA, 2004, Naturally‐occurring CD4+CD25+ immunoregulatory T cells, central players in the arena of peripheral tolerance, 16, 81

10.1146/annurev.immunol.21.120601.141122

10.1111/j.1600-6143.2005.00972.x

10.1038/ni1037

Zenclussen AC, 2005, Abnormal T‐cell reactivity against paternal antigens in spontaneous abortion, adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model, 166, 811

10.1517/14712598.7.9.1301

10.1128/JVI.79.12.7860-7867.2005

10.4049/jimmunol.174.6.3143

10.1182/blood-2006-04-010637

10.4049/jimmunol.170.12.5809

10.1016/j.it.2005.12.006

10.1038/nri727

Karandikar NJ, 1998, Targeting the B7/CD28, CTLA-4 costimulatory system in CNS autoimmune disease, 89, 10

Grohmann U, 1999, IL‐12 acts selectively on CD8 alpha‐ dendritic cells to enhance presentation of a tumor peptide in vivo, J Immunol, 163, 3100, 10.4049/jimmunol.163.6.3100

10.4049/jimmunol.165.3.1357

10.1093/intimm/14.1.65

10.4049/jimmunol.166.1.277

10.4049/jimmunol.171.5.2581

10.1038/ni1124

10.1182/blood-2005-10-4077

Orabona C, 2005, Cutting edge, silencing suppressor of cytokine signaling 3 expression in dendritic cells turns CD28-Ig from immune adjuvant to suppressant, 174, 6582

10.1002/eji.200535289

Mantovani A, 2002, Macrophage polarization, tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes, 23, 549

10.4049/jimmunol.174.2.636

10.1038/sj.cr.7290282

10.1038/sj.cdd.4401073

Muller AJ, 2005, Indoleamine 2,3‐dioxygenase in cancer, targeting pathological immune tolerance with small-molecule inhibitors, 9, 831

10.4049/jimmunol.176.11.6752

10.1002/ijc.10645

10.1038/nm934

10.1038/nm1196

10.1158/0008-5472.CAN-06-2925

10.1016/j.jri.2003.11.003

10.1021/jm0508888

BanerjeeT et al. A key in vivo antitumor mechanism of action of natural product‐based brassinins is inhibition of indoleamine 2 3‐dioxygenase. Oncogene advance online publication 2007; (DOI DOI:10.1038/sj.onc.1210939).

10.1023/A:1021254725842

10.1093/carcin/16.2.399