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Review

Indoleamine 2,3-dioxygenase in cancer: targeting pathological immune tolerance with small-molecule inhibitors

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Pages 831-849 | Published online: 05 Aug 2005

Bibliography

  • COUSSENS LM, WERB Z: Inflammation and cancer. Nature (2002) 420(6917):860–867.
  • PAWELEC G, HEINZEL S, KIESSLING R et al.: Escape mechanismsin tumor immunity: a year 2000 update. Crit. Rev. Oncog (2000) 11(2):97–133.
  • MARINCOLA FM, JAFFEE EM, HICKLIN DJ et al.: Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv. Immunol (2000) 74:181–273.
  • DUNN GP, BRUCE AT, IKEDA H et al.: Cancer immunoediting: from immunosurveillance to tumor escape. Nat. Immunol (2002) 3(11):991–998.
  • SHANKARAN V, IKEDA H, BRUCE AT et al.: IFNy and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature (2001) 410(6832):1107–1111.
  • LEE PP, YEE C, SAVAGE PA et ell.: Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat. Med. (1999) 5(6):677–685.
  • ROMERO P, DUNBAR PR, VALMORI D et al.: Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J. Exp. Med. (1998) 188(9):1641–1650.
  • HANSON HL, DONERMEYER DL, IKEDA H et al.: Eradication of established tumors by CD8+ T cell adoptive immunotherapy. Immunity (2000) 13(2):265–276.
  • HANAHAN D, WEINBERG RA: The hallmarks of cancer. Cell (2000) 100:57–70.
  • COHEN PA, PENG L, KJAERGAARD J et al.: T-cell adoptive therapy of tumors: mechanisms of improved therapeutic performance. Crit. Rev. Immunol (2001) 21(1-3):215–248.
  • ABKEN H, HOMBACH A, HEUSER C et al.: Tuning tumor-specific T-cell activation: a matter of costimulation? Trends Immunol (2002) 23(5):240–245.
  • BOYLAND E, WILLIAMS DC: The metabolism of tryptophan. 2.The metabolism of tryptophan in patients suffering from cancer of the bladder. Biochem. J. (1956) 64(3):578–582.
  • •First report of elevated tryptophan catabolism in cancer patients.
  • IVANOVA VD: Studies on tryptophan metabolites in the blood and urine of patients with leukemia. ProbL GematoL Pereliv. I6wvi. (1959) 4:18–21.
  • IVANOVA VD: Disorders of Tryptophan Metabolism in Leukaemia. Acta Unio. Int. Contra. Cancrum. (1964) 20:1085–1086.
  • AMBANELLI U, RUBINO A: 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. (1962) 5:49–73.
  • CHABNER BA, DEVITA VT, LIVINGSTON DM et al.: Abnormalities of tryptophan metabolism and plasma pyridoxal phosphate in Hodgkin's disease. N Engl. J. Med. (1970) 282(15):838–843.
  • WOLF H, MADSEN PO, PRICE JM: Studies on the metabolism of tryptophan in patients with benign prostatic hypertrophy or cancer of the prostate. Urol. (1968) 100(4):537–543.
  • ROSE DP: Tryptophan metabolism in carcinoma of the breast. Lancet (1967) 1(7484):239–241.
  • KOTAKE Y, MASAYAMA T: Uber den mechanismus der kynurenine-bildung aus tryptophan. Hoppe-Seyler's Z. PhysioL Chem. (1937) 243:237–244.
  • TAYLOR MW, FENG GS: Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. (1991) 5(11):2516–2522.
  • HIGUCHI K, KUNO S, HAYAISHI 0: Enzymatic formation of D-kynurenine. Federation Proc. (1963) 22:243 (abstr.).
  • HIGUCHI K, HAYAISHI 0: Enzymic formation of D-kynurenine from D-tryptophan. Arch. Biochem. Biophys. (1967) 120(2):397–403.
  • •First full report on the isolation of the IDO enzyme.
  • SHIMIZU T, NOMIYAMA S, HIRATA F et al.: Indoleamine 2,3-dioxygenase. Purification and some properties. J. Biol. Chem. (1978) 253(13):4700–4706.
  • WATANABE Y, YOSHIDA R, SONO M et al.: Immunohistochemical localization of indoleamine 2,3-dioxygenase in the argyrophilic cells of rabbit duodenum and thyroid gland. J. Histochem. Cytochem. (1981) 29(5):623–632.
  • SONO M: Enzyme kinetic and spectroscopic studies of inhibitor and effector interactions with indoleamine 2,3-dioxygenase. 2.Evidence for the existence of another binding site in the enzyme for indole derivative effectors. Biochemistry (1989) 28(13):5400–5407.
  • KADOYA A. TONE S, MAEDA H et al:Gene structure of human indoleamine 2,3-dioxygenase. Biochem. Biophys. Res. Commun. (1992) 189(1):530–536.
  • NAJFELD V MENNINGER J, MUHLEMAN D et al.: Localization of indoleamine 2,3-dioxygenase gene (INDO) to chromosome 8p12- > pll by fluorescent in situ hybridization. Cytogenet. Cell Genet. (1993) 64(3-4):231–232.
  • SUZUKI T, IMAI K: Comparative studies of the indoleamine dioxygenase-like myoglobin from the abalone Sulculus diversicolor. Comp. Biochem. Physiol B. Biochem. MoL Biol. (1997) 117(4):599–604.
  • LITTLEJOHN TK, TAKIKAWA 0, TRUSCOTT RJ et al.: Asp274 and his346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase. j Biol. Chem. (2003) 278(32):29525–29531.
  • CARLIN JM, BORDEN EC, SONDEL, PM et al.: Biologic-response-modifier-induced indoleamine 2,3-dioxygenase activity in human peripheral blood mononuclear cell cultures. J. Immunol (1987) 139(7):2414–2418.
  • CARLIN JM, BORDEN EC, SONDEL PM et al.: Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes. J. Leukoc. Biol. (1989) 45(1):29–34.
  • TAKIKAWA O, TAGAWAY, IWAKURAY et al.: Interferon-gamma-dependent/ independent expression of indoleamine 2,3-dioxygenase. Studies with interferon-gamma-knockout mice. Adv. Exp. Med. Biol (1999) 467:553–557.
  • HWU P DU, MX, LAPOINTE R et ell.: Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J. Immunol (2000) 164(7):3596–3599.
  • DU MX, SOTERO-ESTEVA WD, TAYLOR MW: Analysis of transcription factors regulating induction of indoleamine 2,3-dioxygenase by IFN-gamma. J. Interferon Cytokine Res. (2000) 20(2):133–142.
  • CHON SY, HASSANAIN HH, PINE R et al.: Involvement of two regulatory elements in interferon-gamma-regulated expression of human indoleamine 2,3-dioxygenase gene. J. Interferon Cytokine Res. (1995) 15(0:517–526.
  • CHON SY, HASSANAIN HH, GUPTA SL: Cooperative role of interferon regulatory factor 1 and p91 (STAT1) response elements in interferon-gamma-inducible expression of human indoleamine 2,3-dioxygenase gene. J. Biol. Chem. (1996) 271(29):17247–17252.
  • KONAN KV, TAYLOR MW: Importance of the two interferon-stimulated response element (ISRE) sequences in the regulation of the human indoleamine 2,3-dioxygenase gene. J. Biol. Chem. (1996) 271(32):19140–19145.
  • ROBINSON CM, HALE PT, CARLIN JM: The role of IFN-gamma and TNF-alpha-responsive regulatory elements in the synergistic induction of indoleamine dioxygenase. J. Interferon Cytokine Res. (2005) 25(1):20–30.
  • PINE R: Convergence of TNFalpha and IFNgamma signalling pathways through synergistic induction of IRF-1/ISGF-2 is mediated by a composite GAS/kappaB promoter element. Nucleic Acids Res. (1997) 25(21):4346–4354.
  • MELLOR AL, MUNN DH: Tryptophan catabolism and regulation of adaptive immunity. J. Immunol. (2003) 170(12):5809–5813.
  • GROHMANN U, FALLARINO F, PUCCETTI P: Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol (2003) 24(5):242–248.
  • MELLOR AL, MUNN DH: IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol (2004) 4(10):762–774.
  • YOSHIDA R, NUKIWA T, WATANABE Yet al: Regulation of indoleamine 2,3-dioxygenase activity in the small intestine and the epididymis of mice. Arch. Biochem. Biophys. (1980) 203(1):343–351.
  • TAKIKAWA O, YOSHIDA R, KIDO R et al: Tryptophan degradation in mice initiated by indoleamine 2,3-dioxygenase. J. Biol. Chem. (1986) 261(8):3648–3653.
  • MOFFETT JR, NAMBOODIRI MA: Tryptophan and the immune response. Immunol Cell Biol. (2003) 81(4):247–265.
  • YAMAZAKI F, KUROIWA T, TAKIKAWA 0 et al: Human indolylamine 2,3-dioxygenase. Its tissue distribution, and characterization of the placental enzyme. Biochem. J. (1985) 230(3):635–638.
  • SEDLMAYR P, BLASCHITZ A, WINTERSTEIGER R et al: Localization of indoleamine 2,3-dioxygenase in human female reproductive organs and the placenta. MoL Hum. Reprod. (2002) 8(4):385–391.
  • KUDO Y, BOYD CA, SPYROPOULOU I et al: Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta. J. Reprod. Immunol (2004) 61(2):87–98.
  • HONIG A, RIEGER L, KAPP M et al: Indoleamine 2,3-dioxygenase (IDO) expression in invasive extravillous trophoblast supports role of the enzyme for materno-fetal tolerance. J. Reprod. Immunol (2004) 61(2):79–86.
  • YOSHIDA R, URADE Y, NAKATA K et al.: Specific induction of indoleamine 2,3-dioxygenase by bacterial lipopolysaccharide in the mouse lung. Arch. Biochem. Biophys. (1981) 212(2):629–637.
  • HAYAISHI O, RYOTARO Y, TAKIKAWA O et al.: Indoleamine-dioxygenase - a possible biological function. In: Progress in Tryptophan and Serotonin Research, Walter De Gruyter and Co., Berlin, (1984):33–42.
  • PFEFFERKORN ER: Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc. NatL Acad. Sci. USA (1984) 81(3):908–912.
  • CARLIN JM, OZAKI Y, BYRNE GI et al.: Interferons and indoleamine 2,3-dioxygenase: role in antimicrobial and antitumor effects. Experientia (1989) 45(6):535–541.
  • UNO K, SHIMIZU S, IDO M et aL: Direct and indirect effects of interferon on in vivo murine tumor cell growth. Cancer Res. (1985) 45(3):1320–1327.
  • OZAKI Y, EDELSTEIN MP, DUCH DS: Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. Proc. Nail. Acad. Sci. USA (1988) 85(4):1242–1246.
  • TAKIKAWA O, HABARA-OHKUBO A, YOSHIDA R: IFN-gamma is the inducer of indoleamine 2,3-dioxygenase in allografted tumor cells undergoing rejection. J. Immunol. (1990) 145(4):1246–1250.
  • BURKE F, KNOWLES RG, EAST N et aL: The role of indoleamine 2,3-dioxygenase in the anti-tumour activity of human interferon-gamma in vivo. Int. J. Cancer (1995) 60(1):115–122.
  • YU WG, YAIVIAMOTO N, TAKENAKA H et al.: Molecular mechanisms underlying IFN-gamma-mediated tumor growth inhibition induced during tumor immunotherapy with rIL-12.Int. Immunol. (1996) 8(0:855–865.
  • MUNN DH, ZHOU M, ATTWOOD JT et aL: Prevention of allogeneic fetal rejection by tryptophan catabolism. Science (1998) 281:1191–1193.
  • ••Demonstration that IDO activity suppresses maternal T-cell immunity to fetal alloantigens during pregnancy.
  • MUNN DH, SHAFIZADEH E, ATTWOOD JT et al.: Inhibition of T cell proliferation by macrophage tryptophan catabolism. J. Exp. Med. (1999) 189:1363–1372.
  • ••Demonstration that tryptophandepletion by upregulated IDO in human macrophages blocks T-cell proliferation.
  • MUNN DH, ARMSTRONG E: Cytokine regulation of human monocyte differentiation in vitro: the tumor-cytotoxic phenotype induced by macrophage colony-stimulating factor is developmentally regulated by gamma-interferon. Cancer Res. (1993) 53(11):2603–2613.
  • MUNN DH, PRESSEY J, BEALL AC et aL: Selective activation-induced apoptosis of peripheral T cells imposed by macrophages. A potential mechanism of antigen-specific peripheral lymphocyte deletion. J. Immunol. (1996) 156(2):523–532.
  • CADY SG, SONO M: 1-methyl-DL- tryptophan, beta-(3-benzofitrany1)-DL-alanine (the oxygen analog of tryptophan), and beta-13-benzotbfthienyll-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase. Arch. Biochem. Biophys. (1991) 291:326–333.
  • •Identification of 1MT as a competitive inhibitor of the IDO enzyme.
  • KUDO Y, BOYD CA: Characterisation of L-tryptophan transporters in human placenta: a comparison of brush border and basal membrane vesicles. J. PhysioL (2001) 531(Pt 2):405–416.
  • KUDO Y, BOYD CA: The role of L-tryptophan transport in L-tryptophan degradation by indoleamine 2,3-dioxygenase in human placental explants. PhysioL (2001) 531(Pt 2):417–423.
  • GROHMANN U, ORABONA C, FALLARINO F et al.: CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat. Immunol. (2002) 3(11):1097–1101.
  • ••Demonstration that IDO can mediateCTLA-4 tolerisation through B7 'reverse' signalling.
  • TI VOL EA, BORRIELLO F, SCHWEITZER AN et aL: Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.Immunity (1995) 3(5):541–547.
  • WATERHOUSE P, PENNINGER JM, TIMMS E et al.: Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.Science (1995) 270(5238):985–988.
  • TURKA LA, LINSLEY PS, LIN H et al.: T-cell activation by the CD28 ligand B7 is required for cardiac allograft rejection in vivo. Proc. NatL Acad. Sci. USA (1992) 89(22):11102–11105.
  • LI W, LU L, WANG Z et aL: Costimulation blockade promotes the apoptotic death of graft-infiltrating T cells and prolongs survival of hepatic allografts from FLT3L-treated donors. Transplantation (2001) 72(8):1423–1432.
  • LENSCHOW DJ, ZENG Y, THISTLETHWAITE JR et al.: Long-termsurvival of xenogeneic pancreatic islet grafts induced by CTLA41g. Science (1992) 257(5071):789–792.
  • SHARPE AH, FREEMAN GJ: The B7-CD28 superfamily. Nat. Rev. Immunol. (2002) 2(2):116–126.
  • MELLOR AL, BABAN B, CHANDLER P et al.: Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. Immunol. (2003) 171(4):1652–1655.
  • GROHMANN U, BIANCHI R, ORABONA C et al.: Functional plasticity of dendritic cell subsets as mediated by CD40 versus B7 activation. J. Immunol. (2003) 171(5):2581–2587.
  • FALLARINO F, GROHMANN U, HWANG KW et al.: Modulation of tryptophan catabolism by regulatory T cells. Nat. Immunol. (2003) 4(12):1206–1212.
  • MELLOR AL, CHANDLER P, BABAN B et al.: Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int. Immunol. (2004) 16(10):1391–1401.
  • MUNN DH, SHARMA MD, MELLOR AL: Ligation of B7-1/B7-2 byhuman CD4+ T cells triggers indoleamine2,3-dioxygenase activity in dendritic cells.Immunol. (2004) 172(7):4100–4110.
  • ORABONA C, GROHMANN U, BELLADONNA ML et al.: CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86.Nat. ImmunoL (2004) 5(11):1134–1142.
  • KAUFMAN KA, BOWEN JA, TSAI AF et aL: The CTLA-4 gene is expressed in placental fibroblasts. MoL Hum. Reprod. (1999) 5(1):84–87.
  • DE LA MAZA LM, PETERSON EM: Dependence of the in vitro antiproliferative activity of recombinant human gamma-interferon on the concentration of tryptophan in culture media. Cancer Res. (1988) 48(2):346–350.
  • MALIK ST, KNOWLES RG, EAST N et aL: Antitumor activity of gamma-interferon in ascitic and solid tumor models of human ovarian cancer. Cancer Res. (1991) 51(24):6643–6649.
  • BURKE F, SMITH PD, CROMPTON MR et aL: Cytotoxic response of ovarian cancer cell lines to IFN-gamma is associated with sustained induction of IRF-1 and p21 mRNA. Br. J. Cancer (1999) 80(8):1236–1244.
  • ABOAGYE-MATHIESEN G, EBBESEN P, VON DER MAASE H et al.: Interferon gamma regulates a unique set of proteins in fresh human bladder transitional cell carcinomas. Electrophoresis (1999) 20(2):344–348.
  • MELLOR AL, KESKIN DB, JOHNSON T et al.: Cells expressing indoleamine 2,3-dioxygenase inhibit T cell responses. J. ImmunoL (2002) 168(8):3771–3776.
  • UYTTENHOVE C, PILOTTE L, THEATE I et al.: Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med. (2003) 9(10):1269–1274.
  • ••Demonstration that a wide variety oftumor types overexpress IDO and that IDO activity expressed intrinsically in cancer cells can suppress antitumour immunity.
  • GE K, DUHADAWAY J, SAKAMURO D et al.: Losses of the tumor suppressor BIN1 in breast carcinoma are frequent and reflect deficits in programmed cell death capacity. Int. J. Cancer (2000) 85(3):376–383.
  • GE K, MINHAS F, DUHADAWAY J et aL: Loss of heterozygosity and tumor suppressor activity of Bin1 in prostate carcinoma. Int. J. Cancer (2000) 86(2):155–161.
  • GE K, DUHADAWAY J DU Wet aL: Mechanism for elimination of a tumor suppressor: aberrant splicing of a brain-specific exon causes loss of function of Bin1 in melanoma. Proc. Nail. Acad. Sci. USA (1999) 96(17):9689–9694.
  • TAJIRI T, LIU X, THOMPSON PM et al.: Expression of a MYCN-interacting isoform of the tumor suppressor BIN1 is reduced in neuroblastomas with unfavorable biological features. Clin. Cancer Res. (2003) 9(9):3345–3355.
  • MULLER AJ, DUHADAWAY JB, DONOVER PS et al.: Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bird., potentiates cancer chemotherapy. Nat. Med. (2005) 11(3):312–319.
  • ••Demonstration that loss of the anti-cancergene Bin 1 promotes tumour outgrowth through IDO deregulation and that IDO inhibitors can cooperatively enhance chemotherapy.
  • MUNN DH, MELLOR AL: IDO and tolerance to tumors. Trends MoL Med. (2004) 10(1):15–18.
  • FRIBERG M, JENNINGS R, ALSARRAJ M et al.: Indoleamine 2,3- dioxygenase contributes to tumor cell evasion of T cell-mediated rejection. Int. J. Cancer (2002) 101(2):151–155.
  • •Demonstration that IDO activity
  • MUNN DH, SHARMA MD, LEE JR et al.: Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science
  • MUNN DH, SHARMA MD, HOU D et al.: Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J. Clin. Invest. (2004) 114(2):280–290.dendritic cells initiate the immunosuppressive pathway of tryptophan (2004) 173(6):3748–3754.
  • SEO SK, CHOI JH, KIM YH et al.: 4-1BB-mediated immunotherapy of (2004) 10(10):1088–1094.
  • •Demonstration that 4-1BB signaling can
  • SALIH HR, KOSOWSKI SG, HALUSKA VF et al.: Constitutive expression of functional 4-1BB (CD137) ligand on carcinoma cells. J. ImmunoL
  • ZHANG H, MERCHANT MS, CHUA KS et al.: Tumor expression of 4-1BB ligand sustains tumor lytic T cells. Cancer Biol. Ther. (2003) 2(5):579–586.
  • MUNN AL, STEVENSON BJ, GELI MI et al.: end5, end6, and end7: mutations
  • FALLARINO F, GROHMANN U.
  • •Demonstration that certain T cells by cells overexpressing IDO.
  • FRUMENTO G, ROTONDO R, TONETTI M et al.: 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(4):459–468.
  • TERNESS P, BAUER TM, ROSE Let al.: Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J. Exp. Med. (2002) 196(4):447–457.
  • TEICHER BA: Molecular cancer therapeutics: will the promise be fulfilled? In: Molecular cancer therapeutics: strategies for drug discovery and development, GC Prendergast (Ed.): John Wiley & Sons, Inc., Hoboken NJ, (2004):7–40.
  • CARDIFF RD, WELLINGS SR: The comparative pathology of human and mouse mammary glands. J. Mammary Gland Biol. Neoplasia (1999) 4(1):105–122.
  • POLAK L, TURK JL: Reversal of immunological tolerance by cyclophosphamide through inhibition of suppressor cell activity. Nature (1974) 249(458):654–656.Early report of immunological derepression resulting from cydophosphamide treatment.
  • AWWAD M, NORTH RJ: Cyclophosphamide (Cy)-facilitated adoptive immunotherapy of a Cy-resistant tumour. Evidence that Cy permits the expression of adoptive T-cell mediated immunity by removing suppressor T cells rather than by reducing tumour burden. Immunology (1988) 65(1):87–92.
  • MACHIELS JP, REILLY RT, EMENS LA et al.: Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res. (2001) 61(9):3689–3697.Demonstration of cooperativity between vaccine-based immunotherapy and taxane-based chemotherapy in the treatment of autochthonous MMTV-Neu mouse tumours.
  • MASON K, STAAB A. HUNTER N et aL: Enhancement of tumor radioresponse by docetaxel: Involvement of immune system. Int. J. OncoL (2001) 18(3):599–606.
  • YU D, LIU B, TAN M et ell.: Overexpression of c-erbB-2/neu in breast cancer cells confers increased resistance to Taxol via mdr-1-independent mechanisms. Oncogene (1996) 13(6):1359–1365.
  • PAN J, SHE M, XU Z-X et ell.: Farnesyltransferase inhibitors induce DNA damage via reactive oxygen species in human cancer cells. Cancer Res. (2005) 65(9):3671–3681.
  • NOWAK AK, ROBINSON BW, LAKE RA: Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res. (2003) 63(15):4490–4496.
  • •Mechanistic examination of immunotherapy/chemotherapy cooperativity.
  • BEN-EFRAIM S: Immunomodulating anticancer alkylating drugs: targets and mechanisms of activity. Curr. Drug Targets (2001) 2(2):197–212.
  • KLEBANOFF CA, KHONG HT, ANTONY PA et al: Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy. Trends Immunol (2005) 26(2):111–117.
  • LAKE RA, ROBINSON BW: Opinion: Immunotherapy and chemotherapy - a practical partnership. Nat. Rev. Cancer (2005) 5(5):397–405.
  • HIRATA F, HAYAISHI 0: New degradative routes of 5-hydroxytryptophan and serotonin by intestinal tryptophan 2,3-dioxygenase. Biochem. Biophys. Res. Commun. (1972) 47(5):1112–1119.
  • HIRATA F, HAYAISHI 0, TOKUYAMA T et al.: In vitro and in vivo formation of two new metabolites of melatonin. j Biol. Chem. (1974) 249(4):1311–1313.
  • SONO M, TANIGUCHI T, WATANABE Yet al.: Indoleamine 2,3-dioxygenase. Equilibrium studies of the tryptophan binding to the ferric, ferrous, and CO-bound enzymes. J. Biol. Chem. (1980) 255(01339–1345.
  • SONO M, DAWSON JH: Extensive studies of the heme coordination structure of indoleamine 2,3-dioxygenase and of tryptophan binding with magnetic and natural circular dichroism and electron paramagnetic resonance spectroscopy. Biochim. Biophys. Acta (1984) 789(2):170–187.
  • PETERSON AC, MIGAWA MT, MARTIN MM et al: Evaluation of functionalized tryptophan derivatives and related compounds as competitive inhibitors of indoleamine 2,3-dioxygenase. Med. Chem. Res. (1994) 3:531–544.
  • HAMMETT LP: Physical Organic Chemistry; Reaction Rates, Equilibria and Mechanisms. McGraw-Hill, New York, 1970.
  • CHU KC: The quantitative analysis of structure-activity relationships. In: The Basis of Medicinal Chemistry (1), M. E. Wolff (Ed.): Wiley-Interscience, New York, (1980):393–418.
  • MARTIN YC: Quantitative drug design. Marcel Dekker, New York, 1978.
  • SONO M, ROACH MP, COULTER ED et al.: Heme-Containing Oxygenases. Chem. Rev. (1996) 96(7):2841–2888.
  • •Ionic and radical mechanism for IDO reaction proposed.
  • TERENTIS AC, THOMAS SR, TAKIKAWA 0 et al: The heme environment of recombinant human indoleamine 2,3-dioxygenase. Structural properties and substrate-ligand interactions. J. Biol. Chem. (2002) 277(18):15788–15794.
  • •Slightly different ionic mechanism for IDO reaction proposed.
  • SOUTHAN MD, TRUSCOTT, RJW, JAMIE JF et al.: Structural requirements of the competitive binding site of recombinant human indoleamine 2,3-dioxygenase. Med. Chem. Res. (1996) 6(343–52)
  • EGUCHI N, WATANABE Y, KAWANISHI K et al.: Inhibition of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase by beta-carboline and indole derivatives. Arch. Biochem. Biophys. (1984) 232(2):602–609.
  • SALTER M, HAZELWOOD R, POGSON CI et al.: The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat. Biochem. Pharmacol. (1995) 49(10):1435–1442.
  • WATANABE Y, FUJIWARA M, HAYAISHI 0: 2,5-Dihydro-L-phenylalanine: a competitive inhibitor of indoleamine 2,3-dioxygenase. Biochem. Biophys. Res. Commun. (1978) 85(1):273–279.
  • THOMAS SR, SALAHIFAR H, MASHIMA R et al.: Antioxidants inhibit indoleamine 2,3-dioxygenase in IFN-gamma-activated human macrophages: posttranslational regulation by pyrrolidine dithiocarbamate. j Immunol (2001) 166(10):6332–6340.
  • SONO M, CADY SG: Enzyme kinetic and spectroscopic studies of inhibitor and effector interactions with indoleamine 2,3-dioxygenase. 1.Norharman and 4-phenylimidazole binding to the enzyme as inhibitors and heme ligands. Biochemistry (1989) 28(13):5392–5399.
  • PETERSON AC, LA LOGGIA AJ, HAMAKER LK et al.: Evaluation of Substituted 0-Carbolines as Noncompetitive Indoleamine 2,3-Dioxygenase Inhibitors. Med. Chem. Res. (1993) 4:473–482.
  • TENEN SS, HIRSCH JD: 0-Carboline-3-carboxylic acid ethyl ester antagonizes diazepam activity. Nature (1980) 288(5791):609–610.
  • BRAESTRUP C, NIELSEN M, OLSEN CE: Urinary and brain beta-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc. Natl Acad. Sci. USA (1980) 77(4):2288–2292.
  • LIPPKE KP, SCHUNACK WG, WENNING Wet al.: beta-Carbolines as benzodiazepine receptor ligands. 1.Synthesis and benzodiazepine receptor interaction of esters of beta-carboline-3-carboxylic acid. J. Med. Chem. (1983) 26(4):499–503.
  • GUZMAN F, CAIN M, LARSCHEID P et al.: Biomimetic approach to potential benzodiazepine receptor agonists and antagonists. J. Med. Chem. (1984) 27(5):564–570.
  • WIDNER B, WERNER ER, SCHENNACH H et al.: Simultaneous measurement of serum tryptophan and kynurenine by HPLC. Clin. Chem. (1997) 43(12):2424–2426.
  • LATCH A. NEURAUTER G, WIDNER B et al.: More rapid method for simultaneous measurement of tryptophan and kynurenine by HPLC. Clin. Chem. (2002) 48(3):579–581.
  • VIGNAU J, JACQUEMONT MC, LEFORT A et al.: Simultaneous determination of tryptophan and kynurenine in serum by HPLC with UV and fluorescence detection. Biomed. Chromatogr. (2004) 18(10):872–874.
  • BENDER DA, MCCREANOR GM: The preferred route of kynurenine metabolism in the rat. Biochim. Biophys. Acta (1982) 717(1):56–60.
  • GASSE T, MURR C, MEYERSBACH P et al.: Neopterin production and tryptophan degradation in acute Lyme neuroborreliosis versus late Lyme encephalopathy. Eur. Clin. Chem. Clin. Biochem. (1994) 32(9):685–689.
  • FUCHS D, MOLLER AA, REIBNEGGER G et al.: Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus Type 1 infection. Immunol Lett. (1991) 28(3):207–211.
  • GASSE T, WIDNER B, BAIER-BITTERLICH G et al.: In: Neurochemical markers in degenerative disorders and drugaddiction, G. A. Quereshi, H. Parvez, P. Gaudy et al. (eds.), VSP Press, Zeist, (1998):351–382.
  • FUCHS D, HAUSEN A, REIBNEGGER G et al.: Neopterin as a marker for activated cell-mediated immunity: application in HIV infection. Immunol Today (1988) 9(5):150–155.
  • PARDOLL DM: Spinning molecular immunology into successful immunotherapy. Nat. Rev. Immunol (2002) 2(4):227–238.

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