The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells

Oncotarget

Volumn 7, Issue 25, 2016, Pages 37762-37772

  Jochems, Caroline ^a   Fantini, Massimo ^a   Fernando, Romaine I ^a   Kwilas, Anna R ^a   Donahue, Renee N ^a   Lepone, Lauren M ^a   Grenga, Italia ^a   Kim, Young Seung ^a   Brechbiel, Martin W ^a   Gulley, James L ^a   Madan, Ravi A ^a   Heery, Christopher R ^a   Hodge, James W ^a   Newton, Robert ^b   Schlom, Jeffrey ^a   Tsang, Kwong Y ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b Drug Metabolism Pharmacokinetics Clinical Pharmacology   (United States)

Author keywords

3 dioxygenase (IDO); Dendritic cells; IDO inhibitor; Indoleamine 2; T cells; Tregs

Indexed keywords

EPACADOSTAT; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INDOLEAMINE 2,3 DIOXYGENASE; INDOLEAMINE 2,3 DIOXYGENASE 1; INTERLEUKIN 8; KYNURENINE; LIPOPOLYSACCHARIDE; TRYPTOPHAN; TUMOR ANTIGEN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; CANCER VACCINE; INDOLEAMINE 2,3-DIOXYGENASE 1, HUMAN; OXIME; PEPTIDE; SULFONAMIDE;

ARTICLE; CELL MATURATION; CLINICAL TRIAL (TOPIC); CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOLYSIS; CYTOTOXIC T LYMPHOCYTE; DENDRITIC CELL; ENZYME ACTIVITY; FEMALE; HUMAN; HUMAN CELL; IMMUNOGENICITY; IN VITRO STUDY; LYMPHOCYTE ACTIVATION; LYMPHOCYTE FUNCTION; LYMPHOCYTE PROLIFERATION; NATURAL KILLER CELL; PERIPHERAL BLOOD MONONUCLEAR CELL; PHENOTYPE; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE; TUMOR CELL LINE; ADULT; AGED; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG EFFECTS; IMMUNOLOGY; MALE; METABOLISM; MIDDLE AGED; MONONUCLEAR CELL; NORMAL HUMAN; YOUNG ADULT;

ADULT; AGED; CANCER VACCINES; DENDRITIC CELLS; FEMALE; GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; HEALTHY VOLUNTEERS; HUMANS; INDOLEAMINE-PYRROLE 2,3,-DIOXYGENASE; INTERFERON-GAMMA; KYNURENINE; LEUKOCYTES, MONONUCLEAR; LIPOPOLYSACCHARIDES; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; OXIMES; PEPTIDES; PHENOTYPE; SULFONAMIDES; T-LYMPHOCYTES, CYTOTOXIC; TRYPTOPHAN; YOUNG ADULT;

EID: 84978175044     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9326     Document Type: Article

References (47)

1. Mellor AL, Munn DH. Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today. 1999; 20:469-473.
2. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med. 1999; 189:1363-1372.
3. Hwu P, Du MX, Lapointe R, Do M, Taylor MW, Young HA. Indoleamine 2, 3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol. 2000; 164:3596-3599.
4. Bessede A, Gargaro M, Pallotta MT, Matino D, Servillo G, Brunacci C, Bicciato S, Mazza EM, Macchiarulo A, Vacca C, Iannitti R, Tissi L, Volpi C, et al. Aryl hydrocarbon receptor control of a disease tolerance defence pathway. Nature. 2014; 511:184-190.
5. Curti A, Pandolfi S, Valzasina B, Aluigi M, Isidori A, Ferri E, Salvestrini V, Bonanno G, Rutella S, Durelli I, Horenstein AL, Fiore F, Massaia M, et al. Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25-into CD25+ T regulatory cells. Blood. 2007; 109:2871-2877.
6. Chen W, Liang X, Peterson AJ, Munn DH, Blazar BR. The indoleamine 2, 3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J Immunol. 2008; 181:5396-5404.
7. Chung DJ, Rossi M, Romano E, Ghith J, Yuan J, Munn DH, Young JW. Indoleamine 2, 3-dioxygenase-expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells. Blood. 2009; 114:555-563.
8. Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol. 2010; 185:3190-3198.
9. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2, 3-dioxygenase. Nat Med. 2003; 9:1269-1274.
10. Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL. Potential regulatory function of human dendritic cells expressing indoleamine 2, 3-dioxygenase. Science. 2002; 297:1867-1870.
11. Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ, Messina JL, Chandler P, Koni PA, Mellor AL. Expression of indoleamine 2, 3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest. 2004; 114:280-290.
12. Munn DH. Indoleamine 2, 3-dioxygenase, Tregs and cancer. Curr Med Chem. 2011; 18:2240-2246.
13. Brandacher G, Perathoner A, Ladurner R, Schneeberger S, Obrist P, Winkler C, Werner ER, Werner-Felmayer G, Weiss HG, Gobel G, Margreiter R, Konigsrainer A, Fuchs D, et al. Prognostic value of indoleamine 2, 3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res. 2006; 12: 1144-1151.
14. Pan K, Wang H, Chen MS, Zhang HK, Weng DS, Zhou J, Huang W, Li JJ, Song HF, Xia JC. Expression and prognosis role of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma. J Cancer Res Clin Oncol. 2008; 134:1247-1253.
15. 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.
16. 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.
17. Polak ME, Borthwick NJ, Gabriel FG, Johnson P, Higgins B, Hurren J, McCormick D, Jager MJ, Cree IA. Mechanisms of local immunosuppression in cutaneous melanoma. Br J Cancer. 2007; 96:1879-1887.
18. Astigiano S, Morandi B, Costa R, Mastracci L, D'Agostino A, Ratto GB, Melioli G, Frumento G. Eosinophil granulocytes account for indoleamine 2, 3-dioxygenase-mediated immune escape in human nonsmall cell lung cancer. Neoplasia. 2005; 7:390-396.
19. Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP. Indoleamine 2, 3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013; 210:1389-1402.
20. Cady SG, Sono M. 1-Methyl-DL-tryptophan, beta-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and beta-[3-benzo(b)thienyl]-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2, 3-dioxygenase. Arch Biochem Biophys. 1991; 291:326-333.
21. Jackson E, Dees EC, Kauh JS, Harvey RD, Neuger A, Lush R, Antonia SJ, Minton SE, Ismail-Khan R, Han HS, Vahanian NN, Ramsey WJ, Link CJ, et al. A phase I study of indoximod in combination with docetaxel in metastatic solid tumors. 2013 ASCO Annual Meeting. J Clin Oncol. 2013; 31 (suppl; abstr 3026).
22. Soliman H, Antonia S, Sullivan D, Vanahanian N, Link CJ. Overcoming tumor antigen anergy in human malignancies using the novel indeolamine 2, 3-dioxygenase (IDO) enzyme inhibitor, 1-methyl-D-tryptophan (1MT). 2009 ASCO Annual Meeting J Clin Oncol. 2009; 27 (suppl; abstr 3004).
23. Koblish HK, Hansbury MJ, Bowman KJ, Yang G, Neilan CL, Haley PJ, Burn TC, Waeltz P, Sparks RB, Yue EW, Combs AP, Scherle PA, Vaddi K, et al. Hydroxyamidine inhibitors of indoleamine-2, 3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010; 9:489-498.
24. Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M, Waeltz P, Bowman KJ, Polam P, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010; 115:3520-3530.
25. Beatty GL, O'Dwyer PJ, Clark J, Shi JG, Newton RC, Schaub R, Maleski J, Leopold L, Gajewski T. Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the oral inhibitor of indoleamine 2, 3-dioxygenase (IDO1) INCB024360 in patients (pts) with advanced malignancies. 2013 ASCO Annual Meeting. J Clin Oncol. 2013; 31 (suppl; abstr 3025).
26. Newton RC, Scherle PA, Bowman K, Liu X, Beatty GL, O'Dwyer PJ, Gajewski T, Bowman J, Schaub R, Leopold L. Pharmacodynamic assessment of INCB024360, an inhibitor of indoleamine 2, 3-dioxygenase 1 (IDO1), in advanced cancer patients. 2012 ASCO Annual Meeting. J Clin Oncol. 2012; 2012 (suppl;abstr 2500).
27. Jochems C, Tucker JA, Vergati M, Boyerinas B, Gulley JL, Schlom J, Tsang KY. Identification and characterization of agonist epitopes of the MUC1-C oncoprotein. Cancer Immunol Immunother. 2014; 63:161-174.
28. Gibney GT, Hamid O, Gangadhar TC, Lutzky J, Olszanski AJ, Gajewski T, Chmielowski B, Boasberg PD, Zhao Y, Newton RC, Scherle PA, Bowman J, Maleski J, et al. Preliminary results from a phase 1/2 study of INCB024360 combined with ipilimumab (ipi) in patients (pts) with melanoma. 2014 ASCO Annual Meeting. J Clin Oncol. 2014; 32 (suppl; abstr 3010).
29. Spranger S, Koblish HK, Horton B, Scherle PA, Newton R, Gajewski TF. Mechanism of tumor rejection with doublets of CTLA-4, PD-1/PD-L1, or IDO blockade involves restored IL-2 production and proliferation of CD8(+) T cells directly within the tumor microenvironment. J Immunother Cancer. 2014; 2:3.
30. Sorensen RB, Berge-Hansen L, Junker N, Hansen CA, Hadrup SR, Schumacher TN, Svane IM, Becker JC, Thor Straten P, Andersen MH. The immune system strikes back: cellular immune responses against indoleamine 2, 3-dioxygenase. PLoS One. 2009; 4:e6910.
31. Sorensen RB, Hadrup SR, Svane IM, Hjortso MC, Thor Straten P, Andersen MH. Indoleamine 2, 3-dioxygenase specific, cytotoxic T cells as immune regulators. Blood. 2011; 117:2200-2210.
32. Ito H, Ando T, Ando K, Ishikawa T, Saito K, Moriwaki H, Seishima M. Induction of hepatitis B virus surface antigenspecific cytotoxic T lymphocytes can be up-regulated by the inhibition of indoleamine 2, 3-dioxygenase activity. Immunology. 2014; 142:614-623.
33. Cetindere T, Nambiar S, Santourlidis S, Essmann F, Hassan M. Induction of indoleamine 2, 3-dioxygenase by death receptor activation contributes to apoptosis of melanoma cells via mitochondrial damage-dependent ROS accumulation. Cell Signal. 2010; 22:197-211.
34. Ogasawara N, Oguro T, Sakabe T, Matsushima M, Takikawa O, Isobe K, Nagase F. Hemoglobin induces the expression of indoleamine 2, 3-dioxygenase in dendritic cells through the activation of PI3K, PKC, and NF-kappaB and the generation of reactive oxygen species. J Cell Biochem. 2009; 108:716-725.
35. Hansson M, Asea A, Ersson U, Hermodsson S, Hellstrand K. Induction of apoptosis in NK cells by monocyte-derived reactive oxygen metabolites. J Immunol. 1996; 156:42-47.
36. Song H, Park H, Kim YS, Kim KD, Lee HK, Cho DH, Yang JW, Hur DY. L-kynurenine-induced apoptosis in human NK cells is mediated by reactive oxygen species. Int Immunopharmacol. 2011; 11:932-938.
37. Betten A, Dahlgren C, Mellqvist UH, Hermodsson S, Hellstrand K. Oxygen radical-induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin. J Leukoc Biol. 2004; 75:1111-1115.
38. Hellstrand K. Melanoma immunotherapy: a battle against radicals? Trends Immunol. 2003; 24:232-233; author reply 234.
39. Jasperson LK, Bucher C, Panoskaltsis-Mortari A, Taylor PA, Mellor AL, Munn DH, Blazar BR. Indoleamine 2, 3-dioxygenase is a critical regulator of acute graft-versushost disease lethality. Blood. 2008; 111:3257-3265.
40. Baban B, Chandler PR, Sharma MD, Pihkala J, Koni PA, Munn DH, Mellor AL. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol. 2009; 183:2475-2483.
41. Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science. 2003; 299:1033-1036.
42. Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2, 3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood. 2009; 113:6102-6111.
43. Zhai L, Spranger S, Binder DC, Gritsina G, Lauing KL, Giles FJ, Wainwright DA. Molecular pathways: targeting IDO1 and other tryptophan dioxygenases for cancer immunotherapy. Clin Cancer Res. 2015; 21:5427-5433.
44. Tsang KY, Zaremba S, Nieroda CA, Zhu MZ, Hamilton JM, Schlom J. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine. J Natl Cancer Inst. 1995; 87:982-990.
45. Madan RA, Mohebtash M, Arlen PM, Vergati M, Rauckhorst M, Steinberg SM, Tsang KY, Poole DJ, Parnes HL, Wright JJ, Dahut WL, Schlom J, Gulley JL. Ipilimumab and a poxviral vaccine targeting prostatespecific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2012; 13:501-508.
46. Tsang KY, Zhu M, Nieroda CA, Correale P, Zaremba S, Hamilton JM, Cole D, Lam C, Schlom J. Phenotypic stability of a cytotoxic T-cell line directed against an immunodominant epitope of human carcinoembryonic antigen. Clin Cancer Res. 1997; 3:2439-2449.
47. Lepone LM, Donahue RN, Grenga I, Metenou S, Richards J, Heery CR, Gulley JL, Schlom J. Analyses of 123 peripheral human immune cell subsets: defining differences with age and between healthy donors and cancer patients not detected in analysis of standard immune cell types. J Circ Biomark. 2016; 5. doi: 10.5772/62322.