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Protumorigenic Function of Dendritic Cells

  • Anjli Kukreja
Chapter

Abstract

A growing body of evidence suggests a strong role of the tumor microenvironment in shaping up the final outcome of tumor progression. The focus is now on how various stromal components interact with cancer cells to promote tumor growth and metastasis. Infiltration of dendritic cells is a common feature of most human tumors and until recently, these tumor-infiltrating dendritic cells have largely been studied for their immunologic properties. Current studies reveal a more active role of dendritic cells in the microenvironment leading to tumor enhancement, angiogenesis and bone resorption. These observations have tremendous applications for tumor therapy and suggest a need to better understand the ways by which dendritic cells regulate tumor biology in terms of their antigen-presenting as well as tumor-supporting functions including transdifferentiation into other cell types. This review focuses on the protumorigenic effects of dendritic cells in tumor progression that can be targeted to improve cancer therapy.

Keywords

Vascular Endothelial Growth Factor Dendritic Cell Tumor Microenvironment Mantle Cell Lymphoma Multinucleated Giant Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Albert, M. L., Pearce, S. F., Francisco, L. M., Sauter, B., Roy, P., Silverstein, R. L. and Bhardwaj, N. 1998. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med 188:1359–1368.PubMedCrossRefGoogle Scholar
  2. Arron, J. R. and Choi, Y. 2000. Bone versus immune system. Nature 408:535–536.PubMedCrossRefGoogle Scholar
  3. Aspord, C., Pedroza-Gonzalez, A., Gallegos, M., Tindle, S., Burton, E. C., Su, D., Marches, F., Banchereau, J. and Palucka, A. K. 2007. Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J Exp Med 204:1037–1047.PubMedCrossRefGoogle Scholar
  4. Bahlis, N. J., King, A. M., Kolonias, D., Carlson, L. M., Liu, H. Y., Hussein, M. A., Terebelo, H. R., Byrne, G. E., Jr., Levine, B. L., Boise, L. H. and Lee, K. P. 2007. CD28-mediated regulation of multiple myeloma cell proliferation and survival. Blood 109:5002–5010.PubMedCrossRefGoogle Scholar
  5. Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y. J., Pulendran, B. and Palucka, K. 2000. Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811.PubMedCrossRefGoogle Scholar
  6. Bell, D., Chomarat, P., Broyles, D., Netto, G., Harb, G. M., Lebecque, S., Valladeau, J., Davoust, J., Palucka, K. A. and Banchereau, J. 1999. In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 190:1417–1426.PubMedCrossRefGoogle Scholar
  7. Boyle, W. J., Simonet, W. S. and Lacey, D. L. 2003. Osteoclast differentiation and activation. Nature 423:337–342.PubMedCrossRefGoogle Scholar
  8. Buell, J. F., Papaconstantinou, H. T., Skalow, B., Hanaway, M. J., Alloway, R. R. and Woodle, E. S. 2005. De novo colorectal cancer: five-year survival is markedly lower in transplant recipients compared with the general population. Transplant Proc 37:960–961.PubMedCrossRefGoogle Scholar
  9. Carlos, C. A., Dong, H. F., Howard, O. M., Oppenheim, J. J., Hanisch, F. G. and Finn, O. J. 2005. Human tumor antigen MUC1 is chemotactic for immature dendritic cells and elicits maturation but does not promote Th1 type immunity. J Immunol 175:1628–1635.PubMedGoogle Scholar
  10. Caux, C., Ait-Yahia, S., Chemin, K., de Bouteiller, O., Dieu-Nosjean, M. C., Homey, B., Massacrier, C., Vanbervliet, B., Zlotnik, A. and Vicari, A. 2000. Dendritic cell biology and regulation of dendritic cell trafficking by chemokines. Springer Semin Immunopathol 22:345–369.PubMedCrossRefGoogle Scholar
  11. Chabot, V., Reverdiau, P., Iochmann, S., Rico, A., Senecal, D., Goupille, C., Sizaret, P. Y. and Sensebe, L. 2006. CCL5-enhanced human immature dendritic cell migration through the basement membrane in vitro depends on matrix metalloproteinase-9. J Leukoc Biol 79:767–778.PubMedCrossRefGoogle Scholar
  12. Chomarat, P., Banchereau, J., Davoust, J. and Palucka, A. K. 2000. IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol 1:510–514.PubMedCrossRefGoogle Scholar
  13. Condeelis, J. and Pollard, J. W. 2006. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124:263–266.PubMedCrossRefGoogle Scholar
  14. Condeelis, J. and Segall, J. E. 2003. Intravital imaging of cell movement in tumours. Nat Rev Cancer 3:921–930.PubMedCrossRefGoogle Scholar
  15. Conejo-Garcia, J. R., Benencia, F., Courreges, M. C., Kang, E., Mohamed-Hadley, A., Buckanovich, R. J., Holtz, D. O., Jenkins, A., Na, H., Zhang, L., Wagner, D. S., Katsaros, D., Caroll, R. and Coukos, G. 2004. Tumor-infiltrating dendritic cell precursors recruited by a beta-defensin contribute to vasculogenesis under the influence of Vegf-A. Nat Med 10:950–958.PubMedCrossRefGoogle Scholar
  16. Coury, F., Annels, N., Rivollier, A., Olsson, S., Santoro, A., Speziani, C., Azocar, O., Flacher, M., Djebali, S., Tebib, J., Brytting, M., Egeler, R. M., Rabourdin-Combe, C., Henter, J. I., Arico, M. and Delprat, C. 2008. Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion. Nat Med 14:81–87.PubMedCrossRefGoogle Scholar
  17. Coussens, L. M. and Werb, Z. 2002. Inflammation and cancer. Nature 420:860–867.PubMedCrossRefGoogle Scholar
  18. Curiel, T. J., Cheng, P., Mottram, P., Alvarez, X., Moons, L., Evdemon-Hogan, M., Wei, S., Zou, L., Kryczek, I., Hoyle, G., Lackner, A., Carmeliet, P. and Zou, W. 2004. Dendritic cell subsets differentially regulate angiogenesis in human ovarian cancer. Cancer Res 64:5535–5538.PubMedCrossRefGoogle Scholar
  19. D'Amico, G., Bianchi, G., Bernasconi, S., Bersani, L., Piemonti, L., Sozzani, S., Mantovani, A. and Allavena, P. 1998. Adhesion, transendothelial migration, and reverse transmigration of in vitro cultured dendritic cells. Blood 92:207–214.PubMedGoogle Scholar
  20. da Costa, C. E., Annels, N. E., Faaij, C. M., Forsyth, R. G., Hogendoorn, P. C. and Egeler, R. M. 2005. Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis. J Exp Med 201:687–693.PubMedCrossRefGoogle Scholar
  21. de Visser, K. E., Eichten, A. and Coussens, L. M. 2006. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer 6:24–37.PubMedCrossRefGoogle Scholar
  22. Delamarre, L., Pack, M., Chang, H., Mellman, I. and Trombetta, E. S. 2005. Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science 307:1630–1634.PubMedCrossRefGoogle Scholar
  23. Della Bella, S., Gennaro, M., Vaccari, M., Ferraris, C., Nicola, S., Riva, A., Clerici, M., Greco, M. and Villa, M. L. 2003. Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 89:1463–1472.PubMedCrossRefGoogle Scholar
  24. Dembic, Z., Schenck, K. and Bogen, B. 2000. Dendritic cells purified from myeloma are primed with tumor-specific antigen (idiotype) and activate CD4+ T cells. Proc Natl Acad Sci U S A 97:2697–2702.PubMedCrossRefGoogle Scholar
  25. Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J. and Schreiber, R. D. 2002. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998.PubMedCrossRefGoogle Scholar
  26. Enk, A. H., Jonuleit, H., Saloga, J. and Knop, J. 1997. Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int J Cancer 73:309–316.PubMedCrossRefGoogle Scholar
  27. Fernandez Pujol, B., Lucibello, F. C., Zuzarte, M., Lutjens, P., Muller, R. and Havemann, K. 2001. Dendritic cells derived from peripheral monocytes express endothelial markers and in the presence of angiogenic growth factors differentiate into endothelial-like cells. Eur J Cell Biol 80:99–110.PubMedCrossRefGoogle Scholar
  28. Ferrara, N. and Kerbel, R. S. 2005. Angiogenesis as a therapeutic target. Nature 438:967–974.PubMedCrossRefGoogle Scholar
  29. Finn, O. J., Jerome, K. R., Henderson, R. A., Pecher, G., Domenech, N., Magarian-Blander, J. and Barratt-Boyes, S. M. 1995. MUC-1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev 145:61–89.PubMedCrossRefGoogle Scholar
  30. Fujii, S., Shimizu, K., Kronenberg, M. and Steinman, R. M. 2002. Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs. Nat Immunol 3:867–874.PubMedCrossRefGoogle Scholar
  31. Gabrilovich, D. I., Chen, H. L., Girgis, K. R., Cunningham, H. T., Meny, G. M., Nadaf, S., Kavanaugh, D. and Carbone, D. P. 1996. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 2:1096–1103.PubMedCrossRefGoogle Scholar
  32. Ghiringhelli, F., Puig, P. E., Roux, S., Parcellier, A., Schmitt, E., Solary, E., Kroemer, G., Martin, F., Chauffert, B. and Zitvogel, L. 2005. Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med 202:919–929.PubMedCrossRefGoogle Scholar
  33. Giuliani, N., Bataille, R., Mancini, C., Lazzaretti, M. and Barille, S. 2001. Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 98:3527–3533.PubMedCrossRefGoogle Scholar
  34. Gottfried, E., Kreutz, M., Haffner, S., Holler, E., Iacobelli, M., Andreesen, R. and Eissner, G. 2007. Differentiation of human tumour-associated dendritic cells into endothelial-like cells: an alternative pathway of tumour angiogenesis. Scand J Immunol 65:329–335.PubMedCrossRefGoogle Scholar
  35. Grois, N., Prayer, D., Prosch, H. and Lassmann, H. 2005. Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain 128:829–838.PubMedCrossRefGoogle Scholar
  36. Han, J. H., Choi, S. J., Kurihara, N., Koide, M., Oba, Y. and Roodman, G. D. 2001. Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood 97:3349–3353.PubMedCrossRefGoogle Scholar
  37. Han, X., Sterling, H., Chen, Y., Saginario, C., Brown, E. J., Frazier, W. A., Lindberg, F. P. and Vignery, A. 2000. CD47, a ligand for the macrophage fusion receptor, participates in macrophage multinucleation. J Biol Chem 275:37984–37992.PubMedCrossRefGoogle Scholar
  38. Hanahan, D. and Weinberg, R. A. 2000. The hallmarks of cancer. Cell 100:57–70.PubMedCrossRefGoogle Scholar
  39. Hayashi, T., Hideshima, T., Akiyama, M., Raje, N., Richardson, P., Chauhan, D. and Anderson, K. C. 2003. Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes. Blood 102:1435–1442.PubMedCrossRefGoogle Scholar
  40. Heath, W. R., Belz, G. T., Behrens, G. M., Smith, C. M., Forehan, S. P., Parish, I. A., Davey, G. M., Wilson, N. S., Carbone, F. R. and Villadangos, J. A. 2004. Cross-presentation, dendritic cell subsets, and the generation of immunity to cellular antigens. Immunol Rev 199:9–26.PubMedCrossRefGoogle Scholar
  41. Hiltbold, E. M., Vlad, A. M., Ciborowski, P., Watkins, S. C. and Finn, O. J. 2000. The mechanism of unresponsiveness to circulating tumor antigen MUC1 is a block in intracellular sorting and processing by dendritic cells. J Immunol 165:3730–3741.PubMedGoogle Scholar
  42. Hollender, P., Ittelett, D., Villard, F., Eymard, J. C., Jeannesson, P. and Bernard, J. 2002. Active matrix metalloprotease-9 in and migration pattern of dendritic cells matured in clinical grade culture conditions. Immunobiology 206:441–458.PubMedCrossRefGoogle Scholar
  43. Iyengar, P., Combs, T. P., Shah, S. J., Gouon-Evans, V., Pollard, J. W., Albanese, C., Flanagan, L., Tenniswood, M. P., Guha, C., Lisanti, M. P., Pestell, R. G. and Scherer, P. E. 2003. Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and proto-oncogene stabilization. Oncogene 22:6408–6423.PubMedCrossRefGoogle Scholar
  44. Klimp, A. H., Hollema, H., Kempinga, C., van der Zee, A. G., de Vries, E. G. and Daemen, T. 2001. Expression of cyclooxygenase-2 and inducible nitric oxide synthase in human ovarian tumors and tumor-associated macrophages. Cancer Res 61:7305–7309.PubMedGoogle Scholar
  45. Koga, T., Inui, M., Inoue, K., Kim, S., Suematsu, A., Kobayashi, E., Iwata, T., Ohnishi, H., Matozaki, T., Kodama, T., Taniguchi, T., Takayanagi, H. and Takai, T. 2004. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 428:758–763.PubMedCrossRefGoogle Scholar
  46. Koide, N., Nishio, A., Sato, T., Sugiyama, A. and Miyagawa, S. 2004. Significance of macrophage chemoattractant protein-1 expression and macrophage infiltration in squamous cell carcinoma of the esophagus. Am J Gastroenterol 99:1667–1674.PubMedCrossRefGoogle Scholar
  47. Kouwenhoven, M., Ozenci, V., Tjernlund, A., Pashenkov, M., Homman, M., Press, R. and Link, H. 2002. Monocyte-derived dendritic cells express and secrete matrix-degrading metalloproteinases and their inhibitors and are imbalanced in multiple sclerosis. J Neuroimmunol 126:161–171.PubMedCrossRefGoogle Scholar
  48. Krtolica, A., Parrinello, S., Lockett, S., Desprez, P. Y. and Campisi, J. 2001. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci U S A 98:12072–12077.PubMedCrossRefGoogle Scholar
  49. Kukita, T., Wada, N., Kukita, A., Kakimoto, T., Sandra, F., Toh, K., Nagata, K., Iijima, T., Horiuchi, M., Matsusaki, H., Hieshima, K., Yoshie, O. and Nomiyama, H. 2004. RANKL-induced DC-STAMP is essential for osteoclastogenesis. J Exp Med 200:941–946.PubMedCrossRefGoogle Scholar
  50. Kukreja, A., Hutchinson, A., Dhodapkar, K., Mazumder, A., Vesole, D., Angitapalli, R., Jagannath, S. and Dhodapkar, M. V. 2006. Enhancement of clonogenicity of human multiple myeloma by dendritic cells. J Exp Med 203:1859–1865.PubMedCrossRefGoogle Scholar
  51. Kukreja, A., Hutchinson, A., Mazumder, A., Vesole, D., Angitapalli, R., Jagannath, S., O'Connor O. A. and Dhodapkar, M. V. 2007. Bortezomib disrupts tumour-dendritic cell interactions in myeloma and lymphoma: therapeutic implications. Br J Haematol 136:106–110.PubMedCrossRefGoogle Scholar
  52. Laxmanan, S., Robertson, S. W., Wang, E., Lau, J. S., Briscoe, D. M. and Mukhopadhyay, D. 2005. Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways. Biochem Biophys Res Commun 334:193–198.PubMedCrossRefGoogle Scholar
  53. Lewis, C. E., Leek, R., Harris, A. and McGee, J. O. 1995. Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages. J Leukoc Biol 57:747–751.PubMedGoogle Scholar
  54. Lin, E. Y. and Pollard, J. W. 2004. Role of infiltrated leucocytes in tumour growth and spread. Br J Cancer 90:2053–2058.PubMedCrossRefGoogle Scholar
  55. Lissbrant, I. F., Stattin, P., Wikstrom, P., Damber, J. E., Egevad, L. and Bergh, A. 2000. Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival. Int J Oncol 17:445–451.PubMedGoogle Scholar
  56. Lissoni, P., Malugani, F., Bonfanti, A., Bucovec, R., Secondino, S., Brivio, F., Ferrari-Bravo, A., Ferrante, R., Vigore, L., Rovelli, F., Mandala, M., Viviani, S., Fumagalli, L. and Gardani, G. S. 2001. Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1. J Biol Regul Homeost Agents 15:140–144.PubMedGoogle Scholar
  57. Lucas, M., Schachterle, W., Oberle, K., Aichele, P. and Diefenbach, A. 2007. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26:503–517.PubMedCrossRefGoogle Scholar
  58. MacLennan, I. and Vinuesa, C. 2002. Dendritic cells, BAFF, and APRIL: innate players in adaptive antibody responses. Immunity 17:235–238.PubMedCrossRefGoogle Scholar
  59. Menetrier-Caux, C., Montmain, G., Dieu, M. C., Bain, C., Favrot, M. C., Caux, C. and Blay, J. Y. 1998. Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 92:4778–4791.PubMedGoogle Scholar
  60. Moreaux, J., Cremer, F. W., Reme, T., Raab, M., Mahtouk, K., Kaukel, P., Pantesco, V., De Vos, J., Jourdan, E., Jauch, A., Legouffe, E., Moos, M., Fiol, G., Goldschmidt, H., Rossi, J. F., Hose, D. and Klein, B. 2005. The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature. Blood 106:1021–1030.PubMedCrossRefGoogle Scholar
  61. Moreaux, J., Legouffe, E., Jourdan, E., Quittet, P., Reme, T., Lugagne, C., Moine, P., Rossi, J. F., Klein, B. and Tarte, K. 2004. BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood 103:3148–3157.PubMedCrossRefGoogle Scholar
  62. Nestle, F. O., Burg, G., Fah, J., Wrone-Smith, T. and Nickoloff, B. J. 1997. Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen-presenting cells. Am J Pathol 150:641–651.PubMedGoogle Scholar
  63. Novak, A. J., Darce, J. R., Arendt, B. K., Harder, B., Henderson, K., Kindsvogel, W., Gross, J. A., Greipp, P. R. and Jelinek, D. F. 2004. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood 103:689–694.PubMedCrossRefGoogle Scholar
  64. Ohm, J. E. and Carbone, D. P. 2001. VEGF as a mediator of tumor-associated immunodeficiency. Immunol Res 23:263–272.PubMedCrossRefGoogle Scholar
  65. Osman, M., Tortorella, M., Londei, M. and Quaratino, S. 2002. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells. Immunology 105:73–82.PubMedCrossRefGoogle Scholar
  66. Park, S. J., Nakagawa, T., Kitamura, H., Atsumi, T., Kamon, H., Sawa, S., Kamimura, D., Ueda, N., Iwakura, Y., Ishihara, K., Murakami, M. and Hirano, T. 2004. IL-6 regulates in vivo dendritic cell differentiation through STAT3 activation. J Immunol 173:3844–3854.PubMedGoogle Scholar
  67. Pearse, R. N., Sordillo, E. M., Yaccoby, S., Wong, B. R., Liau, D. F., Colman, N., Michaeli, J., Epstein, J. and Choi, Y. 2001. Multiple myeloma disrupts the TRANCE/ osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci U S A 98:11581–11586.PubMedCrossRefGoogle Scholar
  68. Pendl, G. G., Robert, C., Steinert, M., Thanos, R., Eytner, R., Borges, E., Wild, M. K., Lowe, J. B., Fuhlbrigge, R. C., Kupper, T. S., Vestweber, D. and Grabbe, S. 2002. Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1. Blood 99:946–956.PubMedCrossRefGoogle Scholar
  69. Ratta, M., Fagnoni, F., Curti, A., Vescovini, R., Sansoni, P., Oliviero, B., Fogli, M., Ferri, E., Della Cuna, G. R., Tura, S., Baccarani, M. and Lemoli, R. M. 2002. Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 100:230–237.PubMedCrossRefGoogle Scholar
  70. Rettig, M. B., Ma, H. J., Vescio, R. A., Pold, M., Schiller, G., Belson, D., Savage, A., Nishikubo, C., Wu, C., Fraser, J., Said, J. W. and Berenson, J. R. 1997. Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. Science 276:1851–1854.PubMedCrossRefGoogle Scholar
  71. Richardson, P. G. and Anderson, K. C. 2003. Bortezomib: a novel therapy approved for multiple myeloma. Clin Adv Hematol Oncol 1:596–600.PubMedGoogle Scholar
  72. Richardson, P. G., Schlossman, R., Hideshima, T. and Anderson, K. C. 2005. New treatments for multiple myeloma. Oncology (Williston Park) 19:1781–1792; discussion 1792, 1795–1797.Google Scholar
  73. Rivollier, A., Mazzorana, M., Tebib, J., Piperno, M., Aitsiselmi, T., Rabourdin-Combe, C., Jurdic, P. and Servet-Delprat, C. 2004. Immature dendritic cell transdifferentiation into osteoclasts: a novel pathway sustained by the rheumatoid arthritis microenvironment. Blood 104:4029–4037.PubMedCrossRefGoogle Scholar
  74. Said, J. W., Rettig, M. R., Heppner, K., Vescio, R. A., Schiller, G., Ma, H. J., Belson, D., Savage, A., Shintaku, I. P., Koeffler, H. P., Asou, H., Pinkus, G., Pinkus, J., Schrage, M., Green, E. and Berenson, J. R. 1997. Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. Blood 90:4278–4282.PubMedGoogle Scholar
  75. Saito, H., Tsujitani, S., Ikeguchi, M., Maeta, M. and Kaibara, N. 1998. Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer 78:1573–1577.PubMedCrossRefGoogle Scholar
  76. Sandel, M. H., Dadabayev, A. R., Menon, A. G., Morreau, H., Melief, C. J., Offringa, R., van der Burg, S. H., Janssen-van Rhijn, C. M., Ensink, N. G., Tollenaar, R. A., van de Velde, C. J. and Kuppen, P. J. 2005. Prognostic value of tumor-infiltrating dendritic cells in colorectal cancer: role of maturation status and intratumoral localization. Clin Cancer Res 11:2576–2582.PubMedCrossRefGoogle Scholar
  77. Sica, A., Allavena, P. and Mantovani, A. 2008. Cancer related inflammation: The macrophage connection. Cancer Lett 267:204–215.PubMedCrossRefGoogle Scholar
  78. Speziani, C., Rivollier, A., Gallois, A., Coury, F., Mazzorana, M., Azocar, O., Flacher, M., Bella, C., Tebib, J., Jurdic, P., Rabourdin-Combe, C. and Delprat, C. 2007. Murine dendritic cell transdifferentiation into osteoclasts is differentially regulated by innate and adaptive cytokines. Eur J Immunol 37:747–757.PubMedCrossRefGoogle Scholar
  79. Steinbrink, K., Graulich, E., Kubsch, S., Knop, J. and Enk, A. H. 2002. CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood 99:2468–2476.PubMedCrossRefGoogle Scholar
  80. Steinbrink, K., Jonuleit, H., Muller, G., Schuler, G., Knop, J. and Enk, A. H. 1999. Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood 93:1634–1642.PubMedGoogle Scholar
  81. Steinbrink, K., Wolfl, M., Jonuleit, H., Knop, J. and Enk, A. H. 1997. Induction of tolerance by IL-10-treated dendritic cells. J Immunol 159:4772–4780.PubMedGoogle Scholar
  82. Steinman, R. M., Hawiger, D. and Nussenzweig, M. C. 2003. Tolerogenic dendritic cells. Annu Rev Immunol 21:685–711.PubMedCrossRefGoogle Scholar
  83. Sunderkotter, C., Goebeler, M., Schulze-Osthoff, K., Bhardwaj, R. and Sorg, C. 1991. Macrophage-derived angiogenesis factors. Pharmacol Ther 51:195–216.PubMedCrossRefGoogle Scholar
  84. Takahashi, A., Kono, K., Ichihara, F., Sugai, H., Fujii, H. and Matsumoto, Y. 2004. Vascular endothelial growth factor inhibits maturation of dendritic cells induced by lipopolysaccharide, but not by proinflammatory cytokines. Cancer Immunol Immunother 53:543–550.PubMedCrossRefGoogle Scholar
  85. Teitelbaum, S. L. 2000. Bone resorption by osteoclasts. Science 289:1504–1508.PubMedCrossRefGoogle Scholar
  86. Teitelbaum, S. L. and Ross, F. P. 2003. Genetic regulation of osteoclast development and function. Nat Rev Genet 4:638–649.PubMedCrossRefGoogle Scholar
  87. Trombetta, E. S. and Mellman, I. 2005. Cell biology of antigen processing in vitro and in vivo. Annu Rev Immunol 23:975–1028.PubMedCrossRefGoogle Scholar
  88. Tsutsui, S., Yasuda, K., Suzuki, K., Tahara, K., Higashi, H. and Era, S. 2005. Macrophage infiltration and its prognostic implications in breast cancer: the relationship with VEGF expression and microvessel density. Oncol Rep 14:425–431.PubMedGoogle Scholar
  89. Uy, G. L., Trivedi, R., Peles, S., Fisher, N. M., Zhang, Q. J., Tomasson, M. H., DiPersio, J. F. and Vij, R. 2007. Bortezomib inhibits osteoclast activity in patients with multiple myeloma. Clin Lymphoma Myeloma 7:587–589.PubMedCrossRefGoogle Scholar
  90. Vermaelen, K. Y., Cataldo, D., Tournoy, K., Maes, T., Dhulst, A., Louis, R., Foidart, J. M., Noel, A. and Pauwels, R. 2003. Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma. J Immunol 171:1016–1022.PubMedGoogle Scholar
  91. Vicari, A. P., Treilleux, I. and Lebecque, S. 2004. Regulation of the trafficking of tumour-infiltrating dendritic cells by chemokines. Semin Cancer Biol 14:161–169.PubMedCrossRefGoogle Scholar
  92. Yagi, M., Miyamoto, T., Sawatani, Y., Iwamoto, K., Hosogane, N., Fujita, N., Morita, K., Ninomiya, K., Suzuki, T., Miyamoto, K., Oike, Y., Takeya, M., Toyama, Y. and Suda, T. 2005. DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. J Exp Med 202:345–351.PubMedCrossRefGoogle Scholar
  93. Yang, A. S. and Lattime, E. C. 2003. Tumor-induced interleukin 10 suppresses the ability of splenic dendritic cells to stimulate CD4 and CD8 T-cell responses. Cancer Res 63:2150–2157.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Section of HematologyYale UniversityNew HavenUSA

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