Indoleamine 2,3-dioxygenase, an emerging target for anti-cancer therapy

Current Cancer Drug Targets

Volumn 9, Issue 8, 2009, Pages 938-952

  Liu, X ^a   Newton, R C ^a   Friedman, S M ^a   Scherle, P A ^a  

^a Drug Metabolism Pharmacokinetics Clinical Pharmacology   (United States)

Author keywords

Cancer and anti cancer; Dendritic cells; Immune suppression or tolerance; Indoleamine 2,3 dioxygenase; Kynurenine; L tryptophan; T cells

Indexed keywords

1 METHYL DEXTRO TRYPTOPHAN; ANTINEOPLASTIC AGENT; AUTOLOGOUS THERMOSTABLE HEMODERIVATIVE VACCINE; BRASSININ; CANCER VACCINE; CARBOPLATIN; CARMUSTINE; CISPLATIN; D 1 MT; DIINDOLMETHANE; ETOPOSIDE; EXIGUAMINE A; INDOLEAMINE 2,3 DIOXYGENASE; INDOLEAMINE 2,3 DIOXYGENASE INHIBITOR; MENDIONE; METHYLTIOHYDANTOIN TRYPTOPHAN; NSC 401366; PACLITAXEL; TEMOZOLOMIDE; TRYPTOPHAN; UNCLASSIFIED DRUG;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; CANCER INHIBITION; CANCER SURVIVAL; CELLULAR IMMUNITY; CLINICAL TRIAL; DRUG POTENCY; DRUG POTENTIATION; DRUG RESPONSE; ENDOMETRIUM CARCINOMA; ENZYME ACTIVATION; ENZYME INHIBITION; HUMAN; IMMUNOLOGICAL TOLERANCE; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; OVARY CANCER; PROGNOSIS; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTINEOPLASTIC AGENTS; HUMANS; INDOLEAMINE-PYRROLE 2,3,-DIOXYGENASE; NEOPLASMS;

EID: 74849101015     PISSN: 15680096     EISSN: None     Source Type: Journal    
DOI: 10.2174/156800909790192374     Document Type: Review

References (120)

1. Peters, J. C. Tryptophan nutrition and metabolism: an overview. Adv. Exp. Med. Biol. 1991, 294, 345-358.
2. Ruddick, J. P.; Evans, A. K.; Nutt, D. J.; Lightman, S. L.; Rook, G. A.; Lowry, C. A. Tryptophan metabolism in the central nervous system: medical implications. Expert. Rev. Mol. Med. 2006, 8, 1-27.
3. Takikawa, O. Biochemical and medical aspects of the indoleamine 2,3-dioxygenase-initiated L-tryptophan metabolism. Biochem. Biophys. Res. Commun. 2005, 338, 12-19.
4. Higuchi, K.; Hayaishi, O. Enzymic formation of D-kynurenine from D-tryptophan. Arch. Biochem. Biophys. 1967, 120, 397-403.
5. Taylor, M. W.; Feng, G. S. Relationship between interferongamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991, 5, 2516-2522.
6. Mellor, A. L.; Munn, D. H. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 2004, 4, 762-774.
7. Hayaishi, O. Indoleamine 2,3-dioxygenase--with special reference to the mechanism of interferon action. Biken J. 1985, 28, 39-49.
8. Däubener, W.; MacKenzie, C. R. IFN-gamma activated indoleamine 2,3-dioxygenase activity in human cells is an antiparasitic and an antibacterial effector mechanism. Adv. Exp. Med. Biol. 1999, 467, 517-524.
9. Munn, D. H.; Zhou, M.; Attwood, J. T,; Bondarev, I.; Conway, S. J.; Marshall, B.; Brown, C.; Mellor A. L. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 1998, 281, 1191-1193.
10. Kadoya, A.; Tone, S.; Maeda, H.; Minatogawa, Y.; Kido, R. Gene structure of human indoleamine 2,3-dioxygenase. Biochem. Biophys. Res. Commun. 1992, 189, 530-536.
11. Najfeld, V.; Menninger, J.; Muhleman, D.; Comings, D. E.; Gupta, S. L. Localization of indoleamine 2,3-dioxygenase gene (INDO) to chromosome 8p12-->p11 by fluorescent in situ hybridization. Cytogenet Cell Genet. 1993, 64, 231-232.
12. Sugimoto, H.; Oda, S.; Otsuki, T.; Hino, T.; Yoshida, T.; Shiro, Y. Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. Proc. Natl. Acad. Sci. USA 2006, 103, 2611-2616.
13. Macchiarulo, A.; Nuti, R.; Bellocchi, D.; Camaioni, E.; Pellicciari, R. Molecular docking and spatial coarse graining simulations as tools to investigate substrate recognition, enhancer binding and conformational transitions in indoleamine-2,3-dioxygenase (IDO). Biochim. Biophys. Acta. 2007, 1774, 1058-1068.
14. Thomas, S. R.; Stocker, R. Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway. Redox. Rep. 1999, 4, 199-220.
15. Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Heme-Containing Oxygenases. Chem. Rev. 1996, 96, 2841-2888.
16. Shimizu, T.; Nomiyama, S.; Hirata, F.; Hayaishi, O. Indoleamine 2,3-dioxygenase. Purification and some properties. J. Biol. Chem. 1978, 253, 4700-4706.
17. Ball, H. J.; Sanchez-Perez, A.; Weiser, S.; Austin, C. J.; Astelbauer, F.; Miu, J.; McQuillan, J. A.; Stocker, R.; Jermiin, L. S.; Hunt, N. H. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene 2007, 396, 203-213.
18. Ball, H. J.; Yuasa, H. J.; Austin, C. J.; Weiser, S.; Hunt, N. H. Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway. Int. J. Biochem. Cell Biol. 2009, 41, 467-471.
19. Metz, R.; Duhadaway, J. B.; Kamasani, U.; Laury-Kleintop, L.; Muller, A. J.; Prendergast, G. C. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyltryptophan. Cancer Res. 2007, 67, 7082-7087.
20. Lob, S.; Konigsrainer, A.; Schafer, R.; Rammensee, H. G.; Opelz, G.; Terness, P. Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells. Blood 2008, 111, 2152-2154.
21. Qian, F.; Villella, J.; Wallace, P. K.; Mhawech-Fauceglia, P.; Tario, J. D. Jr.; Andrews, C.; Matsuzaki, J.; Valmori, D.; Ayyoub, M.; Frederick, P. J.; Beck, A.; Liao, J.; Cheney, R.; Moysich, K.; Lele, S.; Shrikant, P.; Old, L. J.; Odunsi, K. Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in reversing indoleamine-2,3-dioxygenase-mediated arrest of T-cell proliferation in human epithelial ovarian cancer. Cancer Res. 2009, 69, 5498-5504.
22. Lob, S.; Konigsrainer, A.; Zieker, D.; Brucher, B. L.; Rammensee, H. G.; Opelz, G.; Terness, P. IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol. Immunother. 2009, 58, 153-157.
23. Belladonna, M. L.; Orabona, C.; Grohmann, U.; Puccetti, P. TGFbeta and kynurenines as the key to infectious tolerance. Trends Mol. Med. 2009, 15, 41-49.
24. Baban, B.; Hansen, A. M.; Chandler, P. R.; Manlapat, A.; Bingaman, A.; Kahler, D. J.; Munn, D. H.; Mellor, A. L. A minor population of splenic dendritic cells expressing CD19 mediates IDOdependent T cell suppression via type I IFN signaling following B7 ligation. Int. Immunol. 2005, 17, 909-919.
25. Belladonna, M. L.; Volpi, C.; Bianchi, R.; Vacca, C.; Orabona, C.; Pallotta, M. T.; Boon, L.; Gizzi, S.; Fioretti, M. C.; Grohmann, U.; Puccetti, P. Cutting edge: Autocrine TGF-beta sustains default tolerogenesis by IDO-competent dendritic cells. J. Immunol. 2008, 181, 5194-5198.
26. Braun, D.; Longman, R. S.; Albert, M. L. A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood 2005, 106, 2375-2381.
27. Musso, T.; Gusella, G. L.; Brooks, A.; Longo, D. L.; Varesio, L. Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes. Blood 1994, 83, 1408-1411.
28. MacKenzie, C. R.; González, R. G.; Kniep, E.; Roch, S.; Däubener, W. Cytokine mediated regulation of interferon-gamma-induced IDO activation. Adv. Exp. Med. Biol. 1999, 467, 533-539.
29. Chiarugi, A.; Rovida, E.; Dello Sbarba, P.; Moroni, F. Tryptophan availability selectively limits NO-synthase induction in macrophages. J. Leukoc. Biol. 2003, 73, 172-177.
30. Okamoto, T.; Toné, S.; Kanouchi, H.; Miyawaki, C.; Ono, S.; Minatogawa, Y. Transcriptional regulation of indoleamine 2,3-dioxygenase (IDO) by tryptophan and its analogue : Downregulation of the indoleamine 2,3-dioxygenase (IDO) transcription by tryptophan and its analogue. Cytotechnology 2007, 54, 107-113.
31. Grohmann, U.; Orabona, C.; Fallarino, F.; Vacca, C.; Calcinaro, F.; Falorni, A.; Candeloro, P.; Belladonna, M. L.; Bianchi, R.; Fioretti, M. C.; Puccetti, P. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat. Immunol. 2002, 3, 1097-1101.
32. Tas, S. W.; Vervoordeldonk, M. J.; Hajji, N.; Schuitemaker, J. H.; van der Sluijs, K. F.; May, M. J.; Ghosh, S.; Kapsenberg, M. L.; Tak, P. P.; de Jong, E. C. Noncanonical NF-kappaB signaling in dendritic cells is required for indoleamine 2,3-dioxygenase (IDO) induction and immune regulation. Blood 2007, 110, 1540-1549.
33. Kim, Y. H.; Choi, B. K.; Kang, W. J.; Kim, K. H.; Kang, S. W.; Mellor, A. L.; Munn, D. H.; Kwon, B. S. IFN-{gamma}-indoleamine-2,3 dioxygenase acts as a major suppressive factor in 4-1BB-mediated immune suppression in vivo. J. Leukoc. Biol. 2009, 85, 817-825.
34. Fallarino, F.; Grohmann, U.; Hwang, K. W.; Orabona, C.; Vacca, C.; Bianchi, R.; Belladonna, M. L.; Fioretti, M. C.; Alegre, M. L.; Puccetti, P. Modulation of tryptophan catabolism by regulatory T cells. Nat. Immunol. 2003, 4, 1206-1212.
35. Orabona, C.; Grohmann, U.; Belladonna, M. L.; Fallarino, F.; Vacca, C.; Bianchi, R.; Bozza, S.; Volpi, C.; Salomon, B. L.; Fioretti, M. C.; Romani, L.; Puccetti, P. CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86. Nat. Immunol. 2004, 5, 1134-1142.
36. Fallarino, F.; Vacca, C.; Orabona, C.; Belladonna, M. L.; Bianchi, R.; Marshall, B.; Keskin, D. B.; Mellor, A. L.; Fioretti, M. C.; Grohmann, U.; Puccetti, P. Functional expression of indoleamine 2,3-dioxygenase by murine CD8 alpha(+) dendritic cells. Int. Immunol. 2002, 14, 65-68.
37. Thomas, S. R.; Salahifar, H.; Mashima, R.; Hunt, N. H.; Richardson, D. R.; Stocker, R. Antioxidants inhibit indoleamine 2,3-dioxygenase in IFN-gamma-activated human macrophages: posttranslational regulation by pyrrolidine dithiocarbamate. J. Immunol. 2001, 166, 6332-6340.
38. Orabona, C.; Puccetti, P.; Vacca, C.; Bicciato, S.; Luchini, A.; Fallarino, F.; Bianchi, R.; Velardi, E.; Perruccio, K.; Velardi, A.; Bronte, V.; Fioretti, M. C.; Grohmann, U. Toward the identification of a tolerogenic signature in IDO-competent dendritic cells. Blood 2006, 107, 2846-2854.
39. Orabona, C.; Pallotta, M. T.; Volpi, C.; Fallarino, F.; Vacca, C.; Bianchi, R.; Belladonna, M. L.; Fioretti, M. C.; Grohmann, U.; Puccetti, P. SOCS3 drives proteasomal degradation of indoleamine 2,3-dioxygenase (IDO) and antagonizes IDO-dependent tolerogenesis. Proc. Natl. Acad. Sci. USA 2008, 105, 20828-20833.
40. Munn, D. H.; Shafizadeh, E.; Attwood, J. T.; Bondarev, I.; Pashine, A.; Mellor, A. L. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med. 1999, 189, 1363-1372.
41. Grohmann, U.; Bianchi, R.; Belladonna, M. L.; Silla, S.; Fallarino, F.; Fioretti, M. C.; Puccetti, P. IFN-gamma inhibits presentation of a tumor/self peptide by CD8 alpha- dendritic cells via potentiation of the CD8 alpha+ subset. J. Immunol. 2000, 165, 1357-1363.
42. Grohmann, U.; Bianchi, R.; Orabona, C.; Fallarino, F.; Vacca, C.; Micheletti, A.; Fioretti, M. C.; Puccetti, P. Functional plasticity of dendritic cell subsets as mediated by CD40 versus B7 activation. J. Immunol. 2003, 171, 2581-2587.
43. Fallarino, F.; Bianchi, R.; Orabona, C.; Vacca, C.; Belladonna, M. L.; Fioretti, M. C.; Serreze, D. V.; Grohmann, U.; Puccetti, P. CTLA-4-Ig activates forkhead transcription factors and protects dendritic cells from oxidative stress in nonobese diabetic mice. J. Exp. Med. 2004, 200, 1051-1062.
44. Mellor, A. L.; Baban, B.; Chandler, P.; Marshall, B.; Jhaver, K.; Hansen, A.; Koni, P. A.; Iwashima, M.; Munn, D. H. Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J. Immunol. 2003, 171, 1652-1655.
45. Logan, G. J.; Smyth, C. M.; Earl, J. W.; Zaikina, I.; Rowe, P. B.; Smythe, J. A.; Alexander, I. E. HeLa cells cocultured with peripheral blood lymphocytes acquire an immuno-inhibitory phenotype through up-regulation of indoleamine 2,3-dioxygenase activity. Immunology 2002, 105, 478-487.
46. Orabona, C.; Belladonna, M. L.; Vacca, C.; Bianchi, R.; Fallarino, F.; Volpi, C.; Gizzi, S.; Fioretti, M. C.; Grohmann, U.; Puccetti, P. Cutting edge: silencing suppressor of cytokine signaling 3 expression in dendritic cells turns CD28-Ig from immune adjuvant to suppressant. J. Immunol. 2005, 174, 6582-6586.
47. Hwu, P.; Du, M. X.; Lapointe, R.; Do, M.; Taylor, M. W.; Young, H. A. Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J. Immunol. 2000, 164, 3596-3599.
48. Mellor, A. L.; Keskin, D. B.; Johnson, T.; Chandler, P.; Munn, D. H. Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses. J. Immunol. 2002, 168, 3771-3776.
49. Frumento, G.; Rotondo, R.; Tonetti, M.; Damonte, G.; Benatti, U.; Ferrara, G. B. Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase J. Exp. Med. 2002, 196, 459-468.
50. Fallarino, F.; Grohmann, U.; Vacca, C.; Bianchi, R.; Orabona, C.; Spreca, A.; Fioretti, M. C.; Puccetti, P. T cell apoptosis by tryptophan catabolism. Cell Death Differ. 2002, 9, 1069-1077.
51. Munn, D. H.; Sharma, M. D.; Baban, B.; Harding, H. P.; Zhang, Y.; Ron, D.; Mellor, A. L. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 2005, 22, 633-642.
52. Fallarino, F.; Grohmann, U.; You, S.; McGrath, B. C.; Cavener, D. R.; Vacca, C.; Orabona, C.; Bianchi, R.; Belladonna, M. L.; Volpi, C.; Santamaria, P.; Fioretti, M. C.; Puccetti, P. The combined effects of tryptophan starvation and tryptophan catabolites downregulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J. Immunol. 2006, 176, 6752-6761.
53. Curti, A.; Pandolfi, S.; Valzasina, B.; Aluigi, M.; Isidori, A.; Ferri, E.; Salvestrini, V.; Bonanno, G.; Rutella, S.; Durelli, I.; Horenstein, A. L.; Fiore, F.; Massaia, M.; Colombo, M. P.; Baccarani, M.; Lemoli, R. M. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Blood 2007, 109, 2871-2877.
54. Hill, M.; Tanguy-Royer, S.; Royer, P.; Chauveau, C.; Asghar, K.; Tesson, L.; Lavainne, F.; Rémy, S.; Brion, R.; Hubert, F. X.; Heslan, M.; Rimbert, M.; Berthelot, L.; Moffett, J. R.; Josien, R.; Grégoire, M.; Anegon, I. IDO expands human CD4+CD25high regulatory T cells by promoting maturation of LPS-treated dendritic cells. Eur. J. Immunol. 2007, 37, 3054-3062.
55. Sharma, M. D.; Baban, B.; Chandler, P.; Hou, D. Y.; Singh, N.; Yagita, H.; Azuma, M.; Blazar, B. R.; Mellor, A. L.; Munn, D. H. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J. Clin. Invest. 2007, 117, 2570-2582.
56. Myint, A. M.; Schwarz, M. J.; Steinbusch, H. W.; Leonard, B. E. Neuropsychiatric disorders related to interferon and interleukins treatment. Metab. Brain Dis. 2009, 24, 55-68.
57. Brandacher, G.; Hoeller, E.; Fuchs, D.; Weiss, H. G. Chronic immune activation underlies morbid obesity: is IDO a key player? Curr. Drug Metab. 2007, 8, 289-295.
58. Curti, A.; Trabanelli, S.; Salvestrini, V.; Baccarani, M.; Lemoli, R. M. The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology. Blood 2009, 113, 2394-2401.
59. Quan, J.; Tan, P. H.; MacDonald, A.; Friend, P. J.; Quan, J.; Tan, P. H.; MacDonald, A.; Friend, P. J. Manipulation of indoleamine 2,3-dioxygenase (IDO) for clinical transplantation: promises and challenges. Expert. Opin. Biol. Ther. 2008, 8, 1705-1719.
60. Pertovaara, M.; Raitala, A.; Juonala, M.; Lehtimäki, T.; Huhtala, H.; Oja, S. S.; Jokinen, E.; Viikari, J. S.; Raitakari, O. T.; Hurme, M. Indoleamine 2,3-dioxygenase enzyme activity correlates with risk factors for atherosclerosis: the Cardiovascular Risk in Young Finns Study. Clin. Exp. Immunol. 2007, 148, 106-111.
61. Schroecksnadel, K.; Frick, B.; Winkler, C.; Fuchs, D. Crucial role of interferon-gamma and stimulated macrophages in cardiovascular disease. Curr. Vasc. Pharmacol. 2006, 4, 205-213.
62. Uyttenhove, C.; Pilotte, L.; Theate, I.; Stroobant, V.; Colau, D.; Parmentier, N.; Boon, T.; Van den Eynde, B. J. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med. 2003, 9, 1269-1274.
63. Feder-Mengus, C.; Wyler, S.; Hudolin, T.; Ruszat, R.; Bubendorf, L.; Chiarugi, A.; Pittelli, M.; Weber, W. P.; Bachmann, A.; Gasser, T. C.; Sulser, T.; Heberer, M.; Spagnoli, G. C.; Provenzano, M. High expression of indoleamine 2,3-dioxygenase gene in prostate cancer. Eur. J. Cancer 2008, 44, 2266-2275.
64. Sadun, R. E.; Sachsman, S. M.; Chen, X.; Christenson, K. W.; Morris, W. Z.; Hu, P.; Epstein, A. L. Immune signatures of murine and human cancers reveal unique mechanisms of tumor escape and new targets for cancer immunotherapy. Clin. Cancer Res. 2007, 13, 4016-4025.
65. Schroecksnadel, K.; Winkler, C.; Fuith, L. C.; Fuchs, D. Tryptophan degradation in patients with gynecological cancer correlates with immune activation. Cancer Lett. 2005, 223, 323-329.
66. Nakamura, T.; Shima, T.; Saeki, A.; Hidaka, T.; Nakashima, A.; Takikawa, O.; Saito, S. Expression of indoleamine 2, 3-dioxygenase and the recruitment of Foxp3-expressing regulatory T cells in the development and progression of uterine cervical cancer. Cancer Sci. 2007, 98, 874-881.
67. Astigiano, S.; Morandi, B.; Costa, R.; Mastracci, L.; D'Agostino, A.; Ratto, G. B.; Melioli, G.; Frumento, G. Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune escape in human non-small cell lung cancer. Neoplasia 2005, 7, 390-396.
68. Ino, K.; Yamamoto, E.; Shibata, K.; Kajiyama, H.; Yoshida, N.; Terauchi, M.; Nawa, A.; Nagasaka, T.; Takikawa, O.; Kikkawa, F. Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: its association with disease progression and survival. Clin. Cancer Res. 2008, 14, 2310-2317.
69. Ino, K.; Yoshida, N.; Kajiyama, H.; Shibata, K.; Yamamoto, E.; Kidokoro, K.; Takahashi, N.; Terauchi, M.; Nawa, A.; Nomura, S.; Nagasaka, T.; Takikawa, O.; Kikkawa, F. Indoleamine 2,3-dioxygenase is a novel prognostic indicator for endometrial cancer. Br. J. Cancer 2006, 95, 1555-1561.
70. Brandacher, G.; Perathoner, A.; Ladurner, R.; Schneeberger, S.; Obrist, P.; Winkler, C.; Werner, E. R.; Werner-Felmayer, G.; Weiss, H. G.; Göbel, G.; Margreiter, R.; Königsrainer.; A.; Fuchs, D.; Amberger, A. Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: Effect of tumor infiltrating T cells. Clin. Cancer Res. 2006, 12, 1144-1151.
71. Huang, A,; Fuchs, D.; Widner, B.; Glover, C.; Henderson, D. C.; Allen-Mersh, T. G. Serum trytophan decrease correlates with immune activation and impaired quality of life in colorectal cancer. Br. J. Cancer 2002, 86, 1691-1696.
72. Witkiewicz, A.; Williams, T. K.; Cozzitorto, J.; Durkan, B.; Showalter, S. L.; Yeo, C. J.; Brody, J. R. Expression of indoleamine 2,3-dioxygenase in metastatic pancreatic ductal adenocarcinoma recruits regulatory T cells to avoid immune detection. J. Am. Coll. Surg. 2008, 206, 849-854.
73. Takao, M.; Okamoto, A.; Nikaido, T.; Urashima, M.; Takakura, S.; Saito, M.; Saito, M.; Okamoto, S.; Takikawa, O.; Sasaki, H.; Yasuda, M.; Ochiai, K.; Tanaka, T. Increased synthesis of indoleamine-2,3-dioxygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer. Oncol. Rep. 2007, 17, 1333-1339.
74. Okamoto, A.; Nikaido, T.; Ochiai, K.; Takakura, S.; Saito, M.; Aoki, Y.; Ishii, N.; Yanaihara, N.; Yamada, K.; Takikawa, O.; Kawaguchi, R.; Isonishi, S.; Tanaka, T.; Urashima, M. Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clin. Cancer Res. 2005, 11, 6030-6039.
75. Polak, M. E.; Borthwick, N. J.; Gabriel, F. G.; Johnson, P.; Higgins, B.; Hurren, J.; McCormick, D.; Jager, M. J.; Cree, I. A. Mechanisms of local immunosuppression in cutaneous melanoma. Br. J. Cancer 2007, 96, 1879-1887.
76. Munn, D. H.; Sharma, M. D.; Hou, D.; Baban, B.; Lee, J. R.; Antonia, S. J.; Messina, J. L.; Chandler, P.; Koni, P. A.; Mellor, A. L. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J. Clin. Invest. 2004, 114, 280-290.
77. Lee, J. R.; Dalton, R. R.; Messina, J. L.; Sharma, M. D.; Smith, D. M.; Burgess, R. E.; Mazzella, F.; Antonia, S. J.; Mellor, A. L.; Munn, D. H. Pattern of recruitment of immunoregulatory antigenpresenting cells in malignant melanoma. Lab. Invest. 2003, 83, 1457-1466.
78. Wobser, M.; Voigt, H.; Houben, R.; Eggert, A. O.; Freiwald, M.; Kaemmerer, U.; Kaempgen, E.; Schrama, D.; Becker, J. C. Dendritic cell based antitumor vaccination: impact of functional indoleamine 2,3-dioxygenase expression. Cancer Immunol. Immunother. 2007, 56, 1017-1024.
79. Weinlich, G.; Murr, C.; Richardsen, L.; Winkler, C.; Fuchs, D. Decreased serum tryptophan concentration predicts poor prognosis in malignant melanoma patients. Dermatology 2007, 214, 8-14.
80. Sun, J. X.; Zhang, W. G., Chen, Y. X., Zhao, W. H.; Tian, W.; Yang, Y.; Liu, S. H. Indoleamine 2, 3-dioxygenase expression in cells of human acute monocyte leukemia (M(5)) and acute lymphocyte leukemia and therapeutic effect of its inhibitor 1-methyl tryptophan. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007, 15, 478-482.
81. Curti, A.; Aluigi, M.; Pandolfi, S.; Ferri, E.; Isidori, A.; Salvestrini, V.; Durelli, I.; Horenstein, A. L.; Fiore, F.; Massaia, M.; Piccioli, M.; Pileri, S. A.; Zavatto, E.; D'Addio, A.; Baccarani, M.; Lemoli, R. M. Acute myeloid leukemia cells constitutively express the immunoregulatory enzyme indoleamine 2,3-dioxygenase. Leukemia 2007, 21, 353-255.
82. Corm, S.; Berthon, C.; Imbenotte, M.; Biggio, V.; Lhermitte, M.; Dupont, C.; Briche, I.; Quesnel, B. Indoleamine 2,3-dioxygenase activity of acute myeloid leukemia cells can be measured from patients' sera by HPLC and is inducible by IFN-gamma. Leuk. Res. 2009, 33, 490-494.
83. Hoshi, M.; Ito, H.; Fujigaki, H.; Takemura, M.; Takahashi, T.; Tomita, E.; Ohyama, M.; Tanaka, R.; Saito, K.; Seishima, M. Indoleamine 2,3-dioxygenase is highly expressed in human adult Tcell leukemia/lymphoma and chemotherapy changes tryptophan catabolism in serum and reduced activity. Leuk. Res. 2009, 33, 39-45.
84. Karanikas, V.; Zamanakou, M.; Kerenidi, T.; Dahabreh, J.; Hevas, A.; Nakou, M.; Gourgoulianis, K. I.; Germenis, A. E. Indoleamine 2,3-dioxygenase (IDO) expression in lung cancer. Cancer Biol. Ther. 2007, 6, 1258-1262.
85. Pan, K.; Wang, H.; Chen, M. S.; Zhang, H. K.; Weng, D. S.; Zhou, J., Huang, W.; Li, J. J.; Song, H. F.; Xia, J. C. Expression and prognosis role of indoleamine 2,3-dioxygenase in hepatocellular carcinoma. J. Cancer Res. Clin. Oncol. 2008, 134, 1247-1253.
86. Ishio, T.; Goto, S.; Tahara, K.; Tone, S.; Kawano, K.; Kitano, S. Immunoactivative role of indoleamine 2,3-dioxygenase in human hepatocellular carcinoma. J. Gastroenterol. Hepatol. 2004, 19, 319-326.
87. Riesenberg, R.; Weiler, C.; Spring, O.; Eder, M.; Buchner, A.; Popp, T.; Castro, M.; Kammerer, R.; Takikawa, O.; Hatz, R. A.; Stief, C. G.; Hofstetter, A.; Zimmermann. W. Expression of indoleamine 2,3-dioxygenase in tumor endothelial cells correlates with long-term survival of patients with renal cell carcinoma. Clin. Cancer Res. 2007, 13, 6993-7002.
88. Musajo, L.; Benassi C. A.; Parpajola A. Excretion and isolation of kynurenine and 3-hydroxykynurenine from human pathological urine. Clin. Chim. Acta. 1956, 1, 229-235.
89. Spacek, M. Kynurenine in disease, with particular reference to cancer. Can. Med. Assoc. J. 1955, 73, 198-201.
90. Leklem, J. E.; Brown, R. R. Abnormal tryptophan metabolism in a family with a history of bladder cancer. J. Natl. Cancer Inst. 1976, 56, 1101-1104
91. Wolf, H.; Brown, R. R. Tryptophan metabolism in bladder cancer patients from Copenhagen. Scand. J. Urol. Nephrol. 1979, 13, 143-148.
92. Carlin, J. M.; Ozaki, Y.; Byrne, G. I.; Brown, R. R.; Borden, E. C. Interferons and indoleamine 2,3-dioxygenase: role in antimicrobial and antitumor effects. Experientia 1989, 45, 535-541.
93. Friberg, M.; Jennings, R.; Alsarraj, M.; Dessureault, S.; Cantor, A.; Extermann, M.; Mellor, A. L.; Munn, D. H.; Antonia, S. J. Indoleamine 2,3-dioxygenase contributes to tumor cell evasion of T cell-mediated rejection. Int. J. Cancer 2002, 101, 151-155.
94. Yoshida, N.; Ino, K.; Ishida, Y.; Kajiyama, H.; Yamamoto, E.; Shibata, K.; Terauchi, M.; Nawa, A.; Akimoto, H.; Takikawa, O.; Isobe, K.; Kikkawa, F. Overexpression of indoleamine 2,3-dioxygenase in human endometrial carcinoma cells induces rapid tumor growth in a mouse xenograft model. Clin. Cancer Res. 2008, 14, 7251-7259.
95. Miyazaki, T.; Moritake, K.; Yamada, K.; Hara, N.; Osago, H.; Shibata, T.; Akiyama, Y.; Tsuchiya, M. Indoleamine 2,3-dioxygenase as a new target for malignant glioma therapy. J. Neurosurg. 2009 [Epub ahead of print].
96. Muller, A. J.; DuHadaway, J. B.; Donover, P. S.; Sutanto-Ward, E.; Prendergast, G. C. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat. Med. 2005, 11, 312-319.
97. Ou, X.; Cai, S.; Liu, P.; Zeng, J.; He, Y.; Wu, X.; Du, J. Enhancement of dendritic cell-tumor fusion vaccine potency by indoleamine-pyrrole 2,3-dioxygenase inhibitor, 1-MT. J. Cancer Res. Clin. Oncol. 2008, 134, 525-533.
98. Sharma, M. D.; Hou, D. Y.; Liu, Y.; Koni, P. A.; Metz, R.; Chandler, P.; Mellor, A. L.; He, Y.; Munn, D. H. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 2009, 113, 6102-6111.
99. Zeng, J.; Cai, S.; Yi, Y.; He, Y.; Wang, Z.; Jiang, G.; Li, X.; Du, J. Prevention of spontaneous tumor development in a ret transgenic mouse model by ret peptide vaccination with indoleamine 2,3-dioxygenase inhibitor 1-methyl tryptophan. Cancer Res. 2009, 69, 3963-3970.
100. Gasparri, A. M.; Jachetti, E.; Colombo, B.; Sacchi, A.; Curnis, F.; Rizzardi, G. P.; Traversari, C. ; Bellone, M. ; Corti, A. Critical role of indoleamine 2,3-dioxygenase in tumor resistance to repeated treatments with targeted IFNgamma. Mol. Cancer Ther. 2008, 7, 3859-3866.
101. Zheng, X.; Koropatnick, J.; Li, M.; Zhang, X.; Ling, F.; Ren, X.; Hao, X.; Sun, H.; Vladau, C.; Franek, J. A.; Feng, B.; Urquhart, B. L.; Zhong, R.; Freeman, D. J.; Garcia, B.; Min, W. P. Reinstalling antitumor immunity by inhibiting tumor-derived immunosuppressive molecule IDO through RNA interference. J. Immunol. 2006, 177, 5639-5646.
102. Yen, M. C.; Lin, C. C.; Chen, Y. L.; Huang, S. S.; Yang, H. J.; Chang, C. P.; Lei, H. Y.; Lai, M. D. A novel cancer therapy by skin delivery of indoleamine 2,3-dioxygenase siRNA. Clin. Cancer Res. 2009, 15, 641-649.
103. Http://www.incyte.com/
104. Yue, E. Y.; Bouty, B.; Wayland, B.; Bower, M.; Liu, X.; Leffet, L.; Wang, Q.; Bowman, K. J.; Hansbury, M. J.; Liu, C.; Wei, M.; Li, Y.; Wynn, R.; Burn, T. C.; Koblish, H. K.; Fridman, J. S.; Metcalf, B.; Scherle, P. A.; Combs, A. P. Discovery of potent competitive inhibitors of indoleamine 2,3- dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. 2009, [Epub ahead of print].
105. Hou, D. Y.; Muller, A. J.; Sharma, M. D.; DuHadaway, J.; Banerjee, T.; Johnson, M.; Mellor, A. L.; Prendergast, G. C.; Munn, D. H. Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res. 2007, 67, 792-801.
106. Agaugué, S.; Perrin-Cocon, L.; Coutant, F.; André, P.; Lotteau, V. 1-Methyl-tryptophan can interfere with TLR signaling in dendritic cells independently of IDO activity. J. Immunol. 2006, 177, 2061-2071.
107. Jia, L.; Schweikart, K.; Tomaszewski, J.; Page, J. G.; Noker, P. E.; Buhrow, S. A.; Reid, J. M.; Ames, M. M.; Munn, D. H. Toxicology and pharmacokinetics of 1-methyl-d-tryptophan: absence of toxicity due to saturating absorption. Food Chem. Toxicol. 2008, 46, 203-211.
108. Http://clinicaltrials.gov/ct2/results?term=1-methyl-D-tryptophan
109. Kumar, S.; Jaller, D.; Patel, B.; LaLonde, J. M.; DuHadaway, J. B.; Malachowski, W. P.; Prendergast, G. C.; Muller, A. J. Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase. J. Med. Chem. 2008, 51, 4968-4977.
110. Kumar, S.; Malachowski, W. P.; DuHadaway. J. B.; LaLonde, J. M.; Carroll, P. J.; Jaller, D.; Metz, R.; Prendergast, G. C.; Muller, A. J. Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors. J. Med. Chem. 2008, 51, 1706-1718.
111. Mehta, R. G.; Pezzuto, J. M. Discovery of cancer preventive agents from natural products: from plants to prevention. Curr. Oncol. Rep. 2002, 4, 478-486.
112. Gaspari, P.; Banerjee, T.; Malachowski, W. P.; Muller, A. J.; Prendergast, G. C.; DuHadaway, J.; Bennett, S.; Donovan, A. M. Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors. J. Med. Chem. 2006, 49, 684-692.
113. Banerjee, T.; Duhadaway, J. B.; Gaspari, P.; Sutanto-Ward, E.; Munn, D. H.; Mellor, A. L.; Malachowski, W. P.; Prendergast, G. C.; Muller, A. J. A key in vivo antitumor mechanism of action of natural product-based brassinins is inhibition of indoleamine 2,3-dioxygenase. Oncogene 2008, 27, 2851-2857.
114. Carr, G.; Chung, M. K.; Mauk, A. G.; Andersen, R. J. Synthesis of indoleamine 2,3-dioxygenase inhibitory analogues of the sponge alkaloid exiguamine A. J. Med. Chem. 2008, 51, 2634-2637.
115. Volgraf, M.; Lumb, J. P.; Brastianos, H. C.; Carr, G.; Chung, M. K.; Münzel, M.; Mauk, A. G.; Andersen, R. J.; Trauner, D. Biomimetic synthesis of the IDO inhibitors exiguamine A and B. Nat. Chem. Biol. 2008, 4, 535-537.
116. Brastianos, H. C.; Vottero, E.; Patrick, B. O.; Van Soest, R.; Matainaho, T.; Mauk, A. G.; Andersen, R. J. Exiguamine A, an indoleamine-2,3-dioxygenase (IDO) inhibitor isolated from the marine sponge Neopetrosia exigua. J. Am. Chem. Soc. 2006, 128, 16046-16047.
117. Vottero, E.; Balgi, A.; Woods, K.; Tugendreich, S.; Melese, T.; Andersen, R. J.; Mauk, A. G.; Roberge, M. Inhibitors of human indoleamine 2,3-dioxygenase identified with a target-based screen in yeast. Biotechnol. J. 2006, 1, 282-288.
118. Haynes, N. M.; van der Most, R. G.; Lake, R. A.; Smyth, M. J. Immunogenic anti-cancer chemotherapy as an emerging concept. Curr. Opin. Immunol. 2008, 20, 545-557.
119. Zitvogel, L.; Apetoh, L.; Ghiringhelli, F.; Kroemer, G. Immunological aspects of cancer chemotherapy. Nat. Rev. Immunol. 2008, 8, 59-73
120. Baban, B.; Chandler, P.; McCool, D.; Marshall, B.; Munn, D. H.; Mellor, A. L. Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast giant cells during murine gestation and is maternal genome specific. J. Reprod. Immunol. 2004, 61, 67-77.