Elimination of Dendritic Cells in Cancer



Elimination of mature functional dendritic cells represents one of the most important mechanisms of tumor immune evasion. It includes inhibition of dendritic cell differentiation and maturation as well as a direct induction of apoptosis in dendritic cells or their precursors. Numerous experimental and clinical studies revealed that different factors produced by both tumor and stromal cells, such as VEGF, IL-10, TGF-β, gangliosides and other, could induce apoptotic death of dendritic cells and stimulate spontaneous apoptosis both in vitro and in vivo. Both mechanisms, i.e. suppression of dendritic cell differentiation and dendritic cell apoptosis, can contribute to the reduction of dendritic cell numbers observed in cancer, which was shown to be associated with the tumor progression. Therefore, neutralization of the suppressive tumor microenvironment will allow a proper dendritic cell differentiation from their precursors and protect functionally active dendritic cells from apoptotic death.


Dendritic Cell Dendritic Cell Maturation Secondary Lymphoid Organ Immature Dendritic Cell Dendritic Cell Function 


  1. Alcalay, J., Goldberg, L. H., Wolf, J. E., Jr. and Kripke, M. L. 1989. Variations in the number and morphology of Langerhans' cells in the epidermal component of squamous cell carcinomas. Arch Dermatol 125:917–920.PubMedCrossRefGoogle Scholar
  2. Alcalay, J. and Kripke, M. L. 1991. Antigen-presenting activity of draining lymph node cells from mice painted with a contact allergen during ultraviolet carcinogenesis. J Immunol 146:1717–1721.PubMedGoogle Scholar
  3. Almand, B., Resser, J. R., Lindman, B., Nadaf, S., Clark, J. I., Kwon, E. D., Carbone, D. P. and Gabrilovich, D. I. 2000. Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6:1755–1766.PubMedGoogle Scholar
  4. Balkir, L., Tourkova, I. L., Makarenkova, V. P., Shurin, G. V., Robbins, P. D., Yin, X. M., Chatta, G. and Shurin, M. R. 2004. Comparative analysis of dendritic cells transduced with different anti-apoptotic molecules: sensitivity to tumor-induced apoptosis. J Gene Med 6:537–544.PubMedCrossRefGoogle Scholar
  5. 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
  6. Bellik, L., Gerlini, G., Parenti, A., Ledda, F., Pimpinelli, N., Neri, B. and Pantalone, D. 2006. Role of conventional treatments on circulating and monocyte-derived dendritic cells in colorectal cancer. Clin Immunol 121:74–80.PubMedCrossRefGoogle Scholar
  7. Bellone, G., Carbone, A., Smirne, C., Scirelli, T., Buffolino, A., Novarino, A., Stacchini, A., Bertetto, O., Palestro, G., Sorio, C., Scarpa, A., Emanuelli, G. and Rodeck, U. 2006. Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells. J Immunol 177:3448–3460.PubMedGoogle Scholar
  8. Bonham, C. A., Lu, L., Li, Y., Hoffman, R. A., Simmons, R. L. and Thomson, A. W. 1996. Nitric oxide production by mouse bone marrow-derived dendritic cells: implications for the regulation of allogeneic T cell responses. Transplantation 62:1871–1877.PubMedCrossRefGoogle Scholar
  9. Brune, B., von Knethen, A. and Sandau, K. B. 1999. Nitric oxide (NO): an effector of apoptosis. Cell Death Differ 6:969–975.PubMedCrossRefGoogle Scholar
  10. Chen, S., Akbar, S. M., Tanimoto, K., Ninomiya, T., Iuchi, H., Michitaka, K., Horiike, N. and Onji, M. 2000. Absence of CD83-positive mature and activated dendritic cells at cancer nodules from patients with hepatocellular carcinoma: relevance to hepatocarcinogenesis. Cancer Lett 148:49–57.PubMedCrossRefGoogle Scholar
  11. Cochran, A. J., Morton, D. L., Stern, S., Lana, A. M., Essner, R. and Wen, D. R. 2001. Sentinel lymph nodes show profound downregulation of antigen-presenting cells of the paracortex: implications for tumor biology and treatment. Mod Pathol 14:604–608.PubMedCrossRefGoogle Scholar
  12. Coventry, B. J., Lee, P. L., Gibbs, D. and Hart, D. N. 2002. Dendritic cell density and activation status in human breast cancer -- CD1a, CMRF-44, CMRF-56 and CD-83 expression. Br J Cancer 86:546–551.PubMedCrossRefGoogle Scholar
  13. 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
  14. Duckett, C. S., Li, F., Wang, Y., Tomaselli, K. J., Thompson, C. B. and Armstrong, R. C. 1998. Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c. Mol Cell Biol 18:608–615.PubMedGoogle Scholar
  15. Esche, C., Lokshin, A., Shurin, G. V., Gastman, B. R., Rabinowich, H., Watkins, S. C., Lotze, M. T. and Shurin, M. R. 1999. Tumor's other immune targets: dendritic cells. J Leukoc Biol 66:336–344.PubMedGoogle Scholar
  16. Esche, C., Shurin, G. V., Kirkwood, J. M., Wang, G. Q., Rabinowich, H., Pirtskhalaishvili, G. and Shurin, M. R. 2001. Tumor necrosis factor-alpha-promoted expression of Bcl-2 and inhibition of mitochondrial cytochrome c release mediate resistance of mature dendritic cells to melanoma-induced apoptosis. Clin Cancer Res 7:974s–979s.PubMedGoogle Scholar
  17. Fricke, I. and Gabrilovich, D. I. 2006. Dendritic cells and tumor microenvironment: a dangerous liaison. Immunol Invest 35:459–483.PubMedCrossRefGoogle Scholar
  18. Gabrilovich, D. 2004. Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 4:941–952.PubMedCrossRefGoogle Scholar
  19. 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
  20. Gabrilovich, D. I., Ishida, T., Nadaf, S., Ohm, J. E. and Carbone, D. P. 1999. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin Cancer Res 5:2963–2970.PubMedGoogle Scholar
  21. Gerlini, G., Tun-Kyi, A., Dudli, C., Burg, G., Pimpinelli, N. and Nestle, F. O. 2004. Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic cells in metastatic tumor lesions. Am J Pathol 165:1853–1863.PubMedCrossRefGoogle Scholar
  22. Hasegawa, Y., Takanashi, S., Kanehira, Y., Tsushima, T., Imai, T. and Okumura, K. 2001. Transforming growth factor-beta1 level correlates with angiogenesis, tumor progression, and prognosis in patients with nonsmall cell lung carcinoma. Cancer 91:964–971.PubMedCrossRefGoogle Scholar
  23. Hoffmann, T. K., Muller-Berghaus, J., Ferris, R. L., Johnson, J. T., Storkus, W. J. and Whiteside, T. L. 2002. Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck. Clin Cancer Res 8:1787–1793.PubMedGoogle Scholar
  24. Hou, W. S. and Van Parijs, L. 2004. A Bcl-2-dependent molecular timer regulates the lifespan and immunogenicity of dendritic cells. Nat Immunol 5:583–589.PubMedCrossRefGoogle Scholar
  25. Ishida, T., Oyama, T., Carbone, D. P. and Gabrilovich, D. I. 1998. Defective function of Langerhans cells in tumor-bearing animals is the result of defective maturation from hemopoietic progenitors. J Immunol 161:4842–4851.PubMedGoogle Scholar
  26. Ito, M., Minamiya, Y., Kawai, H., Saito, S., Saito, H., Nakagawa, T., Imai, K., Hirokawa, M. and Ogawa, J. 2006. Tumor-derived TGFbeta-1 induces dendritic cell apoptosis in the sentinel lymph node. J Immunol 176:5637–5643.PubMedGoogle Scholar
  27. Kanto, T., Kalinski, P., Hunter, O. C., Lotze, M. T. and Amoscato, A. A. 2001. Ceramide mediates tumor-induced dendritic cell apoptosis. J Immunol 167:3773–3784.PubMedGoogle Scholar
  28. Katsenelson, N. S., Shurin, G. V., Bykovskaia, S. N., Shogan, J. and Shurin, M. R. 2001. Human small cell lung carcinoma and carcinoid tumor regulate dendritic cell maturation and function. Mod Pathol 14:40–45.PubMedCrossRefGoogle Scholar
  29. Kiertscher, S. M., Luo, J., Dubinett, S. M. and Roth, M. D. 2000. Tumors promote altered maturation and early apoptosis of monocyte-derived dendritic cells. J Immunol 164:1269–1276.PubMedGoogle Scholar
  30. Kim, R., Emi, M., Tanabe, K. and Arihiro, K. 2006. Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res 66:5527–5536.PubMedCrossRefGoogle Scholar
  31. Kobie, J. J., Wu, R. S., Kurt, R. A., Lou, S., Adelman, M. K., Whitesell, L. J., Ramanathapuram, L. V., Arteaga, C. L. and Akporiaye, E. T. 2003. Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. Cancer Res 63:1860–1864.PubMedGoogle Scholar
  32. Ladisch, S., Kitada, S. and Hays, E. F. 1987. Gangliosides shed by tumor cells enhance tumor formation in mice. J Clin Invest 79:1879–1882.PubMedCrossRefGoogle Scholar
  33. Lala, P. K. and Chakraborty, C. 2001. Role of nitric oxide in carcinogenesis and tumour progression. Lancet Oncol 2:149–156.PubMedCrossRefGoogle Scholar
  34. Lanzavecchia, A. and Sallusto, F. 2001. Regulation of T cell immunity by dendritic cells. Cell 106:263–266.PubMedCrossRefGoogle Scholar
  35. Lissoni, P., Bolis, S., Mandala, M., Viviani, S., Pogliani, E. and Barni, S. 1999. Blood concentrations of tumor necrosis factor-alpha in malignant lymphomas and their decrease as a predictor of disease control in response to low-dose subcutaneous immunotherapy with interleukin-2. Int J Biol Markers 14:167–171.PubMedGoogle Scholar
  36. Lu, B. and Finn, O. J. 2008. T-cell death and cancer immune tolerance. Cell Death Differ 15:70–79.PubMedCrossRefGoogle Scholar
  37. Ludewig, B., Graf, D., Gelderblom, H. R., Becker, Y., Kroczek, R. A. and Pauli, G. 1995. Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40-ligand) and TNF-alpha, but strongly enhanced by interleukin-10. Eur J Immunol 25:1943–1950.PubMedCrossRefGoogle Scholar
  38. Lyakh, L. A., Sanford, M., Chekol, S., Young, H. A. and Roberts, A. B. 2005. TGF-beta and vitamin D3 utilize distinct pathways to suppress IL-12 production and modulate rapid differentiation of human monocytes into CD83+ dendritic cells. J Immunol 174:2061–2070.PubMedGoogle Scholar
  39. Maecker, B., Mougiakakos, D., Zimmermann, M., Behrens, M., Hollander, S., Schrauder, A., Schrappe, M., Welte, K. and Klein, C. 2006. Dendritic cell deficiencies in pediatric acute lymphoblastic leukemia patients. Leukemia 20:645–649.PubMedCrossRefGoogle Scholar
  40. Mahnke, K. and Enk, A. H. 2005. Dendritic cells: key cells for the induction of regulatory T cells? Curr Top Microbiol Immunol 293:133–150.PubMedCrossRefGoogle Scholar
  41. Makarenkova, V. P., Shurin, G. V., Tourkova, I. L., Balkir, L., Pirtskhalaishvili, G., Perez, L., Gerein, V., Siegfried, J. M. and Shurin, M. R. 2003. Lung cancer-derived bombesin-like peptides down-regulate the generation and function of human dendritic cells. J Neuroimmunol 145:55–67.PubMedCrossRefGoogle Scholar
  42. Marigo, I., Dolcetti, L., Serafini, P., Zanovello, P. and Bronte, V. 2008. Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev 222:162–179.PubMedCrossRefGoogle Scholar
  43. 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
  44. Moser, M. 2003. Dendritic cells in immunity and tolerance-do they display opposite functions? Immunity 19:5–8.PubMedCrossRefGoogle Scholar
  45. Nagaraj, S. and Gabrilovich, D. I. 2008. Tumor escape mechanism governed by myeloid-derived suppressor cells. Cancer Res 68:2561–2563.PubMedCrossRefGoogle Scholar
  46. Nefedova, Y., Huang, M., Kusmartsev, S., Bhattacharya, R., Cheng, P., Salup, R., Jove, R. and Gabrilovich, D. 2004. Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J Immunol 172:464–474.PubMedGoogle Scholar
  47. Ormandy, L. A., Farber, A., Cantz, T., Petrykowska, S., Wedemeyer, H., Horning, M., Lehner, F., Manns, M. P., Korangy, F. and Greten, T. F. 2006. Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma. World J Gastroenterol 12:3275–3282.PubMedGoogle Scholar
  48. Ouaaz, F., Arron, J., Zheng, Y., Choi, Y. and Beg, A. A. 2002. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity 16:257–270.PubMedCrossRefGoogle Scholar
  49. Palucka, A. K., Ueno, H., Fay, J. W. and Banchereau, J. 2007. Taming cancer by inducing immunity via dendritic cells. Immunol Rev 220:129–150.PubMedCrossRefGoogle Scholar
  50. Peguet-Navarro, J., Sportouch, M., Popa, I., Berthier, O., Schmitt, D. and Portoukalian, J. 2003. Gangliosides from human melanoma tumors impair dendritic cell differentiation from monocytes and induce their apoptosis. J Immunol 170:3488–3494.PubMedGoogle Scholar
  51. Perrotta, C., Falcone, S., Capobianco, A., Camporeale, A., Sciorati, C., De Palma, C., Pisconti, A., Rovere-Querini, P., Bellone, M., Manfredi, A. A. and Clementi, E. 2004. Nitric oxide confers therapeutic activity to dendritic cells in a mouse model of melanoma. Cancer Res 64:3767–3771.PubMedCrossRefGoogle Scholar
  52. Pinzon-Charry, A., Ho, C. S., Maxwell, T., McGuckin, M. A., Schmidt, C., Furnival, C., Pyke, C. M. and Lopez, J. A. 2007. Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer. Br J Cancer 97:1251–1259.PubMedCrossRefGoogle Scholar
  53. Pinzon-Charry, A., Maxwell, T. and Lopez, J. A. 2005. Dendritic cell dysfunction in cancer: a mechanism for immunosuppression. Immunol Cell Biol 83:451–461.PubMedCrossRefGoogle Scholar
  54. Pinzon-Charry, A., Maxwell, T., McGuckin, M. A., Schmidt, C., Furnival, C. and Lopez, J. A. 2006. Spontaneous apoptosis of blood dendritic cells in patients with breast cancer. Breast Cancer Res 8:R5.PubMedCrossRefGoogle Scholar
  55. Pirtskhalaishvili, G., Shurin, G. V., Esche, C., Cai, Q., Salup, R. R., Bykovskaia, S. N., Lotze, M. T. and Shurin, M. R. 2000a. Cytokine-mediated protection of human dendritic cells from prostate cancer-induced apoptosis is regulated by the Bcl-2 family of proteins. Br J Cancer 83:506–513.PubMedCrossRefGoogle Scholar
  56. Pirtskhalaishvili, G., Shurin, G. V., Gambotto, A., Esche, C., Wahl, M., Yurkovetsky, Z. R., Robbins, P. D. and Shurin, M. R. 2000b. Transduction of dendritic cells with Bcl-xL increases their resistance to prostate cancer-induced apoptosis and antitumor effect in mice. J Immunol 165:1956–1964.PubMedGoogle Scholar
  57. Polak, M. E., Borthwick, N. J., Gabriel, F. G., Johnson, P., Higgins, B., Hurren, J., McCormick, D., Jager, M. J. and Cree, I. A. 2007. Mechanisms of local immunosuppression in cutaneous melanoma. Br J Cancer 96:1879–1887.PubMedCrossRefGoogle Scholar
  58. Portielje, J. E., Gratama, J. W., van Ojik, H. H., Stoter, G. and Kruit, W. H. 2003. IL-12: a promising adjuvant for cancer vaccination. Cancer Immunol Immunother 52:133–144.PubMedGoogle Scholar
  59. 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
  60. Sakakura, K., Chikamatsu, K., Takahashi, K., Whiteside, T. L. and Furuya, N. 2006. Maturation of circulating dendritic cells and imbalance of T-cell subsets in patients with squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 55:151–159.PubMedCrossRefGoogle Scholar
  61. Serafini, P., Borrello, I. and Bronte, V. 2006. Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol 16:53–65.PubMedCrossRefGoogle Scholar
  62. Shurin, G. V., Shurin, M. R., Bykovskaia, S., Shogan, J., Lotze, M. T. and Barksdale, E. M., Jr. 2001. Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 61:363–369.PubMedGoogle Scholar
  63. Shurin, M. R. 1996. Dendritic cells presenting tumor antigen. Cancer Immunol Immunother 43:158–164.PubMedCrossRefGoogle Scholar
  64. Shurin, M. R. and Gabrilovich, D. I. 2001. Regulation of dendritic cell system by tumor. Cancer Res Ther Control 11:65–78.Google Scholar
  65. Shurin, M. R., Shurin, G. V. and Chatta, G. S. 2007. Aging and the dendritic cell system: implications for cancer. Crit Rev Oncol Hematol 64:90–105.PubMedCrossRefGoogle Scholar
  66. Shurin, M. R., Shurin, G. V., Lokshin, A., Yurkovetsky, Z. R., Gutkin, D. W., Chatta, G., Zhong, H., Han, B. and Ferris, R. L. 2006. Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic cells: friends or enemies? Cancer Metastasis Rev 25:333–356.PubMedCrossRefGoogle Scholar
  67. Spiegel, S. and Merrill, A. H., Jr. 1996. Sphingolipid metabolism and cell growth regulation. Faseb J 10:1388–1397.PubMedGoogle Scholar
  68. Stanford, A., Chen, Y., Zhang, X. R., Hoffman, R., Zamora, R. and Ford, H. R. 2001. Nitric oxide mediates dendritic cell apoptosis by downregulating inhibitors of apoptosis proteins and upregulating effector caspase activity. Surgery 130:326–332.PubMedCrossRefGoogle Scholar
  69. Steinman, R. M. 2007. Lasker Basic Medical Research Award. Dendritic cells: versatile controllers of the immune system. Nat Med 13:1155–1159.PubMedCrossRefGoogle Scholar
  70. Stene, M. A., Babajanians, M., Bhuta, S. and Cochran, A. J. 1988. Quantitative alterations in cutaneous Langerhans cells during the evolution of malignant melanoma of the skin. J Invest Dermatol 91:125–128.PubMedCrossRefGoogle Scholar
  71. Strobl, H., Bello-Fernandez, C., Riedl, E., Pickl, W. F., Majdic, O., Lyman, S. D. and Knapp, W. 1997. flt3 ligand in cooperation with transforming growth factor-beta1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions. Blood 90:1425–1434.PubMedGoogle Scholar
  72. Tabarkiewicz, J., Rybojad, P., Jablonka, A. and Rolinski, J. 2008. CD1c+ and CD303+ dendritic cells in peripheral blood, lymph nodes and tumor tissue of patients with non-small cell lung cancer. Oncol Rep 19:237–243.PubMedGoogle Scholar
  73. Tourkova, I. L., Shurin, G. V., Chatta, G. S., Perez, L., Finke, J., Whiteside, T. L., Ferrone, S. and Shurin, M. R. 2005. Restoration by IL-15 of MHC class I antigen-processing machinery in human dendritic cells inhibited by tumor-derived gangliosides. J Immunol 175:3045–3052.PubMedGoogle Scholar
  74. Trinchieri, G. 2003. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146.PubMedCrossRefGoogle Scholar
  75. Tschopp, J., Irmler, M. and Thome, M. 1998. Inhibition of fas death signals by FLIPs. Curr Opin Immunol 10:552–558.PubMedCrossRefGoogle Scholar
  76. Umansky, V. and Schirrmacher, V. 2001. Nitric oxide-induced apoptosis in tumor cells. Adv Cancer Res 82:107–131.PubMedCrossRefGoogle Scholar
  77. Wong, B. R., Josien, R., Lee, S. Y., Sauter, B., Li, H. L., Steinman, R. M. and Choi, Y. 1997. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med 186:2075–2080.PubMedCrossRefGoogle Scholar
  78. Yang, T., Witham, T. F., Villa, L., Erff, M., Attanucci, J., Watkins, S., Kondziolka, D., Okada, H., Pollack, I. F. and Chambers, W. H. 2002. Glioma-associated hyaluronan induces apoptosis in dendritic cells via inducible nitric oxide synthase: implications for the use of dendritic cells for therapy of gliomas. Cancer Res 62:2583–2591.PubMedGoogle Scholar
  79. Zhou, L. J. and Tedder, T. F. 1996. CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells. Proc Natl Acad Sci USA 93:2588–2592.PubMedCrossRefGoogle Scholar
  80. Zou, W. 2005. Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5:263–274.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Clinical Cooperation Unit Dermato-Oncology (G300)German Cancer Research CenterIm Neuenheimer Feld 280Germany

Personalised recommendations