Imiquimod inhibits melanoma development by promoting pDC cytotoxic functions and impeding tumor vascularization

Journal of Investigative Dermatology

Volumn 134, Issue 10, 2014, Pages 2551-2561

  Aspord, Caroline ^a,b,c   Tramcourt, Laetitia ^a,b,c   Leloup, Claire ^a,b,c   Molens, Jean Paul ^a,b,c   Leccia, Marie Therese ^b,c,d   Charles, Julie ^b,c,d   Plumas, Joel ^a,b,c  

^a ETABLISSEMENT FRANÇAIS DU SANG   (France)

^b UNIV GRENOBLE ALPES   (France)

^c INSERM   (France)

^d GRENOBLE UNIVERSITY HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENIN; CXCL9 CHEMOKINE; FIBROBLAST GROWTH FACTOR; GRANZYME B; IMIQUIMOD; INTERLEUKIN 21; INTERLEUKIN 8; MONOCYTE CHEMOTACTIC PROTEIN 1; TOLL LIKE RECEPTOR 7; VASCULOTROPIN; AMINOQUINOLINE DERIVATIVE; ANTINEOPLASTIC AGENT; PANCREATIC RIBONUCLEASE; VASCULOTROPIN A;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CELL METABOLISM; CONTROLLED STUDY; DEGRANULATION; DOWN REGULATION; HUMAN; HUMAN CELL; HUMAN TISSUE; MELANOMA; METASTATIC MELANOMA; MIDDLE AGED; MOUSE; MYELOID DENDRITIC CELL; NONHUMAN; PLASMACYTOID DENDRITIC CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; T LYMPHOCYTE; TUMOR GROWTH; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; TUMOR VASCULARIZATION; TUMOR VOLUME; ANIMAL; APOPTOSIS; CASE REPORT; DENDRITIC CELL; DISEASE MODEL; DRUG EFFECTS; DRUG SCREENING; KNOCKOUT MOUSE; METABOLISM; NEOVASCULARIZATION, PATHOLOGIC; NONOBESE DIABETIC MOUSE; PATHOLOGY; SCID MOUSE; SKIN NEOPLASMS; TOPICAL DRUG ADMINISTRATION; TUMOR CELL LINE; VASCULARIZATION;

ADMINISTRATION, TOPICAL; AMINOQUINOLINES; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL LINE, TUMOR; DENDRITIC CELLS; DISEASE MODELS, ANIMAL; DOWN-REGULATION; FIBROBLAST GROWTH FACTORS; HUMANS; INTERLEUKIN-8; MELANOMA; MICE; MICE, INBRED NOD; MICE, KNOCKOUT; MICE, SCID; MIDDLE AGED; NEOVASCULARIZATION, PATHOLOGIC; RIBONUCLEASE, PANCREATIC; SKIN NEOPLASMS; VASCULAR ENDOTHELIAL GROWTH FACTOR A; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84922391749     PISSN: 0022202X     EISSN: 15231747     Source Type: Journal    
DOI: 10.1038/jid.2014.194     Document Type: Article

References (59)

1. Adams S, O'Neill DW, Nonaka D et al. (2008) Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J Immunol 181:776-84
2. Aspord C, Pedroza-Gonzalez A, Gallegos M et al. (2007a) Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4 T cells that facilitate tumor development. J Exp Med 204:1037-47
3. Aspord C, Yu CI, Banchereau J et al. (2007b) Humanized mice for the development and testing of human vaccines. Expert Opin Drug Discov 2:949-60
4. Battaglia A, Buzzonetti A, Baranello C et al. (2013) Interleukin-21 (IL-21) synergizes with IL-2 to enhance T-cell receptor-induced human T-cell proliferation and counteracts IL-2/transforming growth factor-betainduced regulatory T-cell development. Immunology 139:109-20
5. Bong AB, Bonnekoh B, Franke I et al. (2002) Imiquimod, a topical immune response modifier, in the treatment of cutaneous metastases of malignant melanoma. Dermatology 205:135-8
6. Cao W, Liu YJ (2007) Innate immune functions of plasmacytoid dendritic cells. Curr Opin Immunol 19:24-30
7. Chaperot L, Blum A, Manches O et al. (2006) Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells. J Immunol 176:248-55
8. Charles J, Di Domizio J, Salameire D et al. (2010) Characterization of circulating dendritic cells in melanoma: role of CCR6 in plasmacytoid dendritic cell recruitment to the tumor. J Invest Dermatol 130:1646-56
9. Colonna M, Trinchieri G, Liu YJ (2004) Plasmacytoid dendritic cells in immunity. Nat Immunol 5:1219-26
10. Drobits B, Holcmann M, Amberg N et al. (2012) Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumorkilling effector cells. J Clin Invest 122:575-85
11. Dummer R, Hauschild A, Becker JC et al. (2008) An exploratory study of systemic administration of the toll-like receptor-7 agonist 852A in patients with refractory metastatic melanoma. Clin Cancer Res 14:856-64
12. Furumoto K, Soares L, Engleman EG et al. (2004) Induction of potent antitumor immunity by in situ targeting of intratumoral DCs. J Clin Invest 113:774-83
13. Gaspari AA (2007) Mechanism of action and other potential roles of an immune response modifier. Cutis 79:36-45
14. Geisse J, Caro I, Lindholm J et al. (2004) Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 50:722-33
15. Gibson SJ, Lindh JM, Riter TR et al. (2002) Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod. Cell Immunol 218:74-86
16. Graeven U, Rodeck U, Karpinski S et al. (2001) Modulation of angiogenesis and tumorigenicity of human melanocytic cells by vascular endothelial growth factor and basic fibroblast growth factor. Cancer Res 61:7282-90
17. Green DS, Dalgleish AG, Belonwu N et al. (2008) Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes and restore the Th1/Th2 balance in patients with metastatic melanoma. Br J Dermatol 159:606-14
18. Harlin H, Meng Y, Peterson AC et al. (2009) Chemokine expression in melanoma metastases associated with CD8 T-cell recruitment. Cancer Res 69:3077-85
19. Hemmi H, Kaisho T, Takeuchi O et al. (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196-200
20. Hensbergen PJ, Wijnands PG, Schreurs MW et al. (2005) The CXCR3 targeting chemokine CXCL11 has potent antitumor activity in vivo involving attraction of CD8 T lymphocytes but not inhibition of angiogenesis. J Immunother 28:343-51
21. Hesling C, D'Incan M, Mansard S et al. (2004) In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases. Br J Dermatol 150:761-7
22. Hristov M, Erl W, Weber PC (2003) Endothelial progenitor cells: mobilization, differentiation, and homing. Arterioscler Thromb Vasc Biol 23:1185-9
23. Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987-95
24. Jahrsdorfer B, Vollmer A, Blackwell SE et al. (2010) Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell expansion. Blood 115:1156-65
25. Jensen TO, Schmidt H, Moller HJ et al. (2012) Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma. Cancer 118:2476-85
26. Kalb ML, Glaser A, Stary G et al. (2012) TRAIL() human plasmacytoid dendritic cells kill tumor cells in vitro: mechanisms of imiquimod-and IFN-alpha-mediated antitumor reactivity. J Immunol 188:1583-91
27. Karrich JJ, Jachimowski LC, Nagasawa M et al. (2013) IL-21-stimulated human plasmacytoid dendritic cells secrete granzyme B, which impairs their capacity to induce T-cell proliferation. Blood 121:3103-11
28. Lande R, Gilliet M (2010) Plasmacytoid dendritic cells: key players in the initiation and regulation of immune responses. Ann N Y Acad Sci 1183:89-103
29. Liu C, Lou Y, Lizee G et al. (2008) Plasmacytoid dendritic cells induce NK celldependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J Clin Invest 118:1165-75
30. Matsui T, Connolly JE, Michnevitz M et al. (2009) CD2 distinguishes two subsets of human plasmacytoid dendritic cells with distinct phenotype and functions. J Immunol 182:6815-23
31. Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172:2731-8
32. Molenkamp BG, van Leeuwen PA, Meijer S et al. (2007) Intradermal CpG-B activates both plasmacytoid and myeloid dendritic cells in the sentinel lymph node of melanoma patients. Clin Cancer Res 13:2961-9
33. Narayan R, Nguyen H, Bentow JJ et al. (2012) Immunomodulation by imiquimod in patients with high-risk primary melanoma. J Invest Dermatol 132:163-9
34. Naylor MF, Chen WR, Teague TK et al. (2006) In situ photoimmunotherapy: a tumour-directed treatment for melanoma. Br J Dermatol 155:1287-92
35. Nukiwa M, Andarini S, Zaini J et al. (2006) Dendritic cells modified to express fractalkine/CX3CL1 in the treatment of preexisting tumors. Eur J Immunol 36:1019-27
36. Palamara F, Meindl S, Holcmann M et al. (2004) Identification and characterization of pDC-like cells in normal mouse skin and melanomas treated with imiquimod. J Immunol 173:3051-61
37. Park YK, Shin DJ, Cho D et al. (2012) Interleukin-21 increases direct cytotoxicity and IFN-gamma production of ex vivo expanded NK cells towards breast cancer cells. Anticancer Res 32:839-46
38. Pashenkov M, Goess G, Wagner C et al. (2006) Phase II trial of a toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma. J Clin Oncol 24:5716-24
39. Petrella TM, Tozer R, Belanger K et al. (2012) Interleukin-21 has activity in patients with metastatic melanoma: a phase II study. J Clin Oncol 30:3396-401
40. Prins RM, Craft N, Bruhn KW et al. (2006) The TLR-7 agonist, imiquimod, enhances dendritic cell survival and promotes tumor antigen-specific T cell priming: relation to central nervous system antitumor immunity. J Immunol 176:157-64
41. Ribatti D (2004) The involvement of endothelial progenitor cells in tumor angiogenesis. J Cell Mol Med 8:294-300
42. Riedel F, Gotte K, Bergler W et al. (2000) Expression of basic fibroblast growth factor protein and its down-regulation by interferons in head and neck cancer. Head Neck 22:183-9
43. Rothenfusser S, Hornung V, Ayyoub M et al. (2004) CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8 T-cell responses in vitro. Blood 103:2162-9
44. Salio M, Cella M, Vermi W et al. (2003) Plasmacytoid dendritic cells prime IFN-gamma-secreting melanoma-specific CD8 lymphocytes and are found in primary melanoma lesions. Eur J Immunol 33:1052-62
45. Schon MP, Wienrich BG, Drewniok C et al. (2004) Death receptorindependent apoptosis in malignant melanoma induced by the smallmolecule immune response modifier imiquimod. J Invest Dermatol 122: 1266-76
46. Seok J, Warren HS, Cuenca AG et al. (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci USA 110:3507-12
47. Sgadari C, Angiolillo AL, Tosato G (1996) Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10. Blood 87:3877-82
48. Shultz LD, Brehm MA, Garcia-Martinez JV et al. (2012) Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol 12:786-98
49. Sidky YA, Borden EC (1987) Inhibition of angiogenesis by interferons: effects on tumor-and lymphocyte-induced vascular responses. Cancer Res 47:5155-61
50. Smits EL, Ponsaerts P, Berneman ZN et al. (2008) The use of TLR7 and TLR8 ligands for the enhancement of cancer immunotherapy. Oncologist 13:859-75
51. Speiser DE, Lienard D, Rufer N et al. (2005) Rapid and strong human CD8 T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest 115:739-46
52. Stanley MA (2002) Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential. Clin Exp Dermatol 27:571-7
53. Stary G, Bangert C, Tauber M et al. (2007) Tumoricidal activity of TLR7/8-activated inflammatory dendritic cells. J Exp Med 204:1441-51
54. Steinmann A, Funk JO, Schuler G et al. (2000) Topical imiquimod treatment of a cutaneous melanoma metastasis. J Am Acad Dermatol 43:555-6
55. Thyrell L, Erickson S, Zhivotovsky B et al. (2002) Mechanisms of Interferonalpha induced apoptosis in malignant cells. Oncogene 21:1251-62
56. Turksma AW, Bontkes HJ, Ruizendaal JJ et al. (2013) Increased cytotoxic capacity of tumor antigen specific human T cells after in vitro stimulation with IL21 producing dendritic cells. Human Immunol 74:506-13
57. Ugurel S, Rappl G, Tilgen W et al. (2001) Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. J Clin Oncol 19:577-83
58. Vermi W, Bonecchi R, Facchetti F et al. (2003) Recruitment of immature plasmacytoid dendritic cells (plasmacytoid monocytes) and myeloid dendritic cells in primary cutaneous melanomas. J Pathol 200:255-68
59. Zeitouni NC, Dawson K, Cheney RT (2005) Treatment of cutaneous metastatic melanoma with imiquimod 5% cream and the pulsed-dye laser. Br J Dermatol 152:376-7