Table of Contents Author Guidelines Submit a Manuscript
Journal of Oncology
Volume 2012 (2012), Article ID 103298, 11 pages
http://dx.doi.org/10.1155/2012/103298
Research Article

Toll-Like Receptor 7 Agonist Therapy with Imidazoquinoline Enhances Cancer Cell Death and Increases Lymphocytic Infiltration and Proinflammatory Cytokine Production in Established Tumors of a Renal Cell Carcinoma Mouse Model

1Department of Urology, Weill Medical College of Cornell University, New York, NY 10065, USA
2Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
3Smith Institute of Urology, North Shore-Long Island Jewish Health System, New Hyde Park, NY 11042, USA

Received 1 October 2011; Accepted 14 November 2011

Academic Editor: Dirk Rades

Copyright © 2012 Eric C. Kauffman et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Jemal, R. Siegel, J. Xu, and E. Ward, “Cancer statistics, 2010,” CA Cancer Journal for Clinicians, vol. 60, no. 5, pp. 277–300, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. M. Sun, R. Thuret, F. Abdollah et al., “Age-adjusted incidence, mortality, and survival rates of stage-specific renal cell carcinoma in North America: a trend analysis,” European Urology, vol. 59, no. 1, pp. 135–141, 2011. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. R. J. Motzer, M. Mazumdar, J. Bacik, W. Berg, A. Amsterdam, and J. Ferrara, “Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma,” Journal of Clinical Oncology, vol. 17, no. 8, pp. 2530–2540, 1999. View at Google Scholar
  4. R. J. Motzer, B. I. Rini, R. M. Bukowski et al., “Sunitinib in patients with metastatic renal cell carcinoma,” Journal of the American Medical Association, vol. 295, no. 21, pp. 2516–2524, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. M. J. Ratain, T. Eisen, W. M. Stadler et al., “Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma,” Journal of Clinical Oncology, vol. 24, no. 16, pp. 2505–2512, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. S. Z. Freed, J. P. Halperin, and M. Gordon, “Idiopathic regression of metastases from renal cell carcinoma,” Journal of Urology, vol. 118, no. 4, pp. 538–542, 1977. View at Google Scholar · View at Scopus
  7. Medical Research Council Renal Cancer Collaborators, “Interferon-α and survival in metastatic renal carcinoma: early results of a randomised controlled trial,” The Lancet, vol. 353, no. 9146, pp. 14–17, 1999. View at Publisher · View at Google Scholar
  8. D. F. McDermott, “Update on the application of interleukin-2 in the treatment of renal cell carcinoma,” Clinical Cancer Research, vol. 13, no. 2, pp. 716s–719s, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. J. H. Finke, P. Rayman, L. Hart et al., “Characterization of tumor-infiltrating lymphocyte subsets from human renal cell carcinoma: specific reactivity defined by cytotoxicity, interferon-γ secretion, and proliferation,” Journal of Immunotherapy, vol. 15, no. 2, pp. 91–104, 1994. View at Google Scholar
  10. C. J. M. Melief and W. M. Kast, “T-cell immunotherapy of cancer,” Research in Immunology, vol. 142, no. 5-6, pp. 425–429, 1991. View at Google Scholar · View at Scopus
  11. L. Yang and D. P. Carbone, “Tumor-host immune interactions and dendritic cell dysfunction,” Advances in Cancer Research, vol. 92, pp. 13–27, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. J. H. Finke, A. H. Zea, J. Stanley et al., “Loss of T-cell receptor ζ chain and p56(lck) in T-cells infiltrating human renal cell carcinoma,” Cancer Research, vol. 53, no. 23, pp. 5613–5616, 1993. View at Google Scholar · View at Scopus
  13. J. Idoyaga, J. Moreno, and L. Bonifaz, “Tumor cells prevent mouse dendritic cell maturation induced by TLR ligands,” Cancer Immunology, Immunotherapy, vol. 56, no. 8, pp. 1237–1250, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. S. Uematsu and S. Akira, “Toll-like receptors and type I Interferons,” Journal of Biological Chemistry, vol. 282, no. 21, pp. 15319–15324, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. H. Hemmi, T. Kaisho, O. Takeuchi et al., “Small-antiviral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway,” Nature Immunology, vol. 3, no. 2, pp. 196–200, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  16. C. Bourquin, C. Hotz, D. Noerenberg et al., “Systemic cancer therapy with a small molecule agonist of toll-like receptor 7 can be improved by circumventing TLR tolerance,” Cancer Research, vol. 71, no. 15, pp. 5123–5133, 2011. View at Publisher · View at Google Scholar · View at PubMed
  17. E. Stockfleth, U. Trefzer, C. Garcia-Bartels, T. Wegner, T. Schmook, and W. Sterry, “The use of Toll-like receptor-7 agonist in the treatment of basal cell carcinoma: an overview,” British Journal of Dermatology, vol. 149, no. 66, supplement, pp. 53–56, 2003. View at Google Scholar
  18. N. B. Butchi, S. Pourciau, M. Du, T. W. Morgan, and K. E. Peterson, “Analysis of the neuroinflammatory response to TLR7 stimulation in the brain: comparison of multiple TLR7 and/or TLR8 agonists,” Journal of Immunology, vol. 180, no. 11, pp. 7604–7612, 2008. View at Google Scholar · View at Scopus
  19. C. Astry, W. Birmachu, L. I. Harrison, and T. C. Meng, “Cutaneous pharmacodynamics of a toll-like receptor 7 agonist, 852A, in humans,” Journal of Clinical Pharmacology, vol. 48, no. 6, pp. 755–762, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. M. F. Naylor, N. Crowson, R. Kuwahara et al., “Treatment of lentigo maligna with topical imiquimod,” British Journal of Dermatology, vol. 149, no. 66, supplement, pp. 66–69, 2003. View at Google Scholar · View at Scopus
  21. S. F. Rajpar and J. R. Marsden, “Imiquimod in the treatment of lentigo maligna,” British Journal of Dermatology, vol. 155, no. 4, pp. 653–656, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. J. Utikal, A. Zimpfer, A. Thoelke et al., “Complete remission of multiple satellite and in-transit melanoma metastases after sequential treatment with isolated limb perfusion and topical imiquimod,” British Journal of Dermatology, vol. 155, no. 2, pp. 488–491, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. E. B. Smith, M. Schwartz, H. Kawamoto et al., “Antitumor effects of imidazoquinolines in urothelial cell carcinoma of the bladder,” Journal of Urology, vol. 177, no. 6, pp. 2347–2351, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. M. J. Schwartz, H. Liu, D. H. Hwang, H. Kawamoto, and D. S. Scherr, “Antitumor effects of an imidazoquinoline in renal cell carcinoma,” Urology, vol. 73, no. 5, pp. 1156–1162, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. A. H. Enk, H. Jonuleit, J. Saloga, and J. Knop, “Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma,” International Journal of Cancer, vol. 73, no. 3, pp. 309–316, 1997. View at Publisher · View at Google Scholar · View at Scopus
  26. D. I. Gabrilovich, J. Corak, I. F. Ciernik, D. Kavanaugh, and D. P. Carbone, “Decreased antigen presentation by dendritic cells in patients with breast cancer,” Clinical Cancer Research, vol. 3, no. 3, pp. 483–490, 1997. View at Google Scholar · View at Scopus
  27. T. Ishida, T. Oyama, D. P. Carbone, and D. I. Gabrilovich, “Defective function of langerhans cells in tumor-bearing animals is the result of defective maturation from hemopoietic progenitors,” Journal of Immunology, vol. 161, no. 9, pp. 4842–4851, 1998. View at Google Scholar · View at Scopus
  28. F. O. Nestle, G. Burg, J. Fäh, T. Wrone-Smith, and B. J. Nickoloff, “Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen- presenting cells,” American Journal of Pathology, vol. 150, no. 2, pp. 641–651, 1997. View at Google Scholar · View at Scopus
  29. I. Daurkin, E. Eruslanov, T. Stoffs et al., “Tumor-associated macrophages mediate immunosuppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 pathway,” Cancer Research, vol. 71, no. 20, pp. 6400–6409, 2011. View at Publisher · View at Google Scholar · View at PubMed
  30. R. H. Thompson, M. D. Gillett, J. C. Cheville et al., “Costimulatory B7-H1 in renal cell carcinoma patients: indicator of tumor aggressiveness and potential therapeutic target,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 49, pp. 17174–17179, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. M. P. Schön and M. Schön, “Immune modulation and apoptosis induction: two sides of the antitumoral activity of imiquimod,” Apoptosis, vol. 9, no. 3, pp. 291–298, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. N. L. Strominger, R. Brady, G. Gullikson, and D. O. Carpenter, “Imiquimod-elicited emesis is mediated by the area postrema, but not by direct neuronal activation,” Brain Research Bulletin, vol. 55, no. 3, pp. 445–451, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. C. C. N. Wu, T. Hayashi, K. Takabayashi et al., “Immunotherapeutic activity of a conjugate of a Toll-like receptor 7 ligand,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 10, pp. 3990–3995, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. M. Schön and M. P. Schön, “The antitumoral mode of action of imiquimod and other imidazoquinolines,” Current Medicinal Chemistry, vol. 14, no. 6, pp. 681–687, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. P. Redondo, J. Del Olmo, A. López-Diaz De Cerio et al., “Imiquimod enhances the systemic immunity attained by local cryosurgery destruction of melanoma lesions,” Journal of Investigative Dermatology, vol. 127, no. 7, pp. 1673–1680, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. E. S. Abdel-Hady, P. Martin-Hirsh, M. Duggan-Keen et al., “Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy,” Cancer Research, vol. 61, no. 1, pp. 192–196, 2001. View at Google Scholar · View at Scopus
  37. S. H. Van Der Burg, S. J. Piersma, A. De Jong et al., “Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 29, pp. 12087–12092, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. U. Winters, S. Daayana, J. T. Lear et al., “Clinical and immunologic results of a phase II trial of sequential imiquimod and photodynamic therapy for vulval intraepithelial neoplasia,” Clinical Cancer Research, vol. 14, no. 16, pp. 5292–5299, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  39. S. Daayana, E. Elkord, U. Winters et al., “Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia,” British Journal of Cancer, vol. 102, no. 7, pp. 1129–1136, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. N. A. Forward, S. J. Furlong, Y. Yang, T. J. Lin, and D. W. Hoskin, “Signaling through TLR7 enhances the immunosuppressive activity of murine CD4+CD25+ T regulatory cells,” Journal of Leukocyte Biology, vol. 87, no. 1, pp. 117–125, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  41. H. Lu, W. M. Wagner, E. Gad et al., “Treatment failure of a TLR-7 agonist occurs due to self-regulation of acute inflammation and can be overcome by IL-10 blockade,” Journal of Immunology, vol. 184, no. 9, pp. 5360–5367, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. R. A. Clark, S. J. Huang, G. F. Murphy et al., “Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells,” Journal of Experimental Medicine, vol. 205, no. 10, pp. 2221–2234, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus