Advertisement

Changes in Dendritic Cells in Cancer and Aging

  • Annabelle Grolleau-Julius
  • Raymond L. Yung
Chapter

Abstract

The majority of common cancers preferentially affect the older population. However, despite the recognized role of dendritic cells in cancer immunotherapy, relatively little is known about the consequence of aging on these important cells. Recent studies have revealed that dendritic cells from old hosts exhibit significant functional defects at multiple levels. These changes may provide a mechanistic basis for the disappointing results of dendritic cell-based immunotherapy in older cancer patients. There is clearly a need to improve our knowledge on how aging modulates these parameters to optimally exploit DC in anticancer vaccines.

Keywords

Dendritic Cell Dendritic Cell Vaccine Dendritic Cell Function Dendritic Cell Vaccination Dendritic Cell Migration 
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. Agrawal, A., Agrawal, S., Cao, J. N., Su, H., Osann, K. and Gupta, S. 2007a. Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol 178:6912–6922.PubMedGoogle Scholar
  2. Agrawal, A., Agrawal, S. and Gupta, S. 2007b. Dendritic cells in human aging. Exp Gerontol 42:421–426.PubMedCrossRefGoogle Scholar
  3. Agrawal, A., Agrawal, S., Tay, J. and Gupta, S. 2008. Biology of dendritic cells in aging. J Clin Immunol 28:14–20.PubMedCrossRefGoogle Scholar
  4. Asavaroengchai, W., Kotera, Y. and Mule, J. J. 2002. Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery. Proc Natl Acad Sci USA 99:931–936.PubMedCrossRefGoogle Scholar
  5. Banchereau, J. and Palucka, A. K. 2005. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5:296–306.PubMedCrossRefGoogle Scholar
  6. Banchereau, J. and Steinman, R. M. 1998. Dendritic cells and the control of immunity. Nature 392:245–252.PubMedCrossRefGoogle Scholar
  7. Bhushan, M., Cumberbatch, M., Dearman, R. J., Andrew, S. M., Kimber, I. and Griffiths, C. E. 2002. Tumour necrosis factor-alpha-induced migration of human Langerhans cells: the influence of ageing. Br J Dermatol 146:32–40.PubMedCrossRefGoogle Scholar
  8. Bhushan, M., Cumberbatch, M., Dearman, R. J., Kimber, I. and Griffiths, C. E. 2004. Exogenous interleukin-1beta restores impaired Langerhans cell migration in aged skin. Br J Dermatol 150:1217–1218.PubMedCrossRefGoogle Scholar
  9. Chiu, B. C., Stolberg, V. R., Zhang, H. and Chensue, S. W. 2007. Increased Foxp3(+) Treg cell activity reduces dendritic cell co-stimulatory molecule expression in aged mice. Mech Ageing Dev 128:618–627.PubMedCrossRefGoogle Scholar
  10. Cumberbatch, M., Dearman, R. J. and Kimber, I. 2002. Influence of ageing on Langerhans cell migration in mice: identification of a putative deficiency of epidermal interleukin-1beta. Immunology 105:466–477.PubMedCrossRefGoogle Scholar
  11. Della Bella, S., Bierti, L., Presicce, P., Arienti, R., Valenti, M., Saresella, M., Vergani, C. and Villa, M. L. 2007. Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol 122:220–228.PubMedCrossRefGoogle Scholar
  12. Donnini, A., Argentati, K., Mancini, R., Smorlesi, A., Bartozzi, B., Bernardini, G. and Provinciali, M. 2002. Phenotype, antigen-presenting capacity, and migration of antigen-presenting cells in young and old age. Exp Gerontol 37:1097–1112.PubMedCrossRefGoogle Scholar
  13. Flamand, V., Sornasse, T., Thielemans, K., Demanet, C., Bakkus, M., Bazin, H., Tielemans, F., Leo, O., Urbain, J. and Moser, M. 1994. Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo. Eur J Immunol 24:605–610.PubMedCrossRefGoogle Scholar
  14. Flood, P. M., Liu, X., Alexander, R., Schreiber, H. and Haque, S. 1998. Loss of resistance to a highly immunogenic tumor with age corresponds to the decline of CD8 T cell activity. J Immunother 21:307–316.PubMedCrossRefGoogle Scholar
  15. Geijtenbeek, T. B., Torensma, R., van Vliet, S. J., van Duijnhoven, G. C., Adema, G. J., van Kooyk, Y. and Figdor, C. G. 2000. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100:575–585.PubMedCrossRefGoogle Scholar
  16. Gijzen, K., Tacken, P. J., Zimmerman, A., Joosten, B., de Vries, I. J., Figdor, C. G. and Torensma, R. 2007. Relevance of DC-SIGN in DC-induced T cell proliferation. J Leukoc Biol 81:729–740.PubMedCrossRefGoogle Scholar
  17. Grolleau, A., Sloan, A. and Mule, J. J. 2005. Dendritic cell-based vaccines for cancer therapy. Cancer Treat Res 123:181–205.PubMedCrossRefGoogle Scholar
  18. Grolleau-Julius, A., Garg, M. R., Mo, R., Stoolman, L. L. and Yung, R. L. 2006. Effect of aging on bone marrow-derived murine CD11c+CD4-CD8alpha-dendritic cell function. J Gerontol A Biol Sci Med Sci 61:1039–1047.PubMedCrossRefGoogle Scholar
  19. Julius, A., Harning, E., Abernathy, L., and Yung, R. L. 2008. Impaired dendritic cell function in aging leads to defective antitumor immunity. Cancer Res 68:6341–6349.PubMedCrossRefGoogle Scholar
  20. Komatsubara, S., Cinader, B. and Muramatsu, S. 1986a. Functional competence of dendritic cells of ageing C57BL/6 mice. Scand J Immunol 24:517–525.PubMedCrossRefGoogle Scholar
  21. Komatsubara, S., Cinader, B. and Muramatsu, S. 1986b. Polymorphism of age-related changes in stimulatory capacity of murine dendritic cells. Mech Ageing Dev 37:163–173.PubMedCrossRefGoogle Scholar
  22. Linton, P. J., Li, S. P., Zhang, Y., Bautista, B., Huynh, Q. and Trinh, T. 2005. Intrinsic versus environmental influences on T-cell responses in aging. Immunol Rev 205:207–219.PubMedCrossRefGoogle Scholar
  23. Lung, T. L., Saurwein-Teissl, M., Parson, W., Schonitzer, D. and Grubeck-Loebenstein, B. 2000. Unimpaired dendritic cells can be derived from monocytes in old age and can mobilize residual function in senescent T cells. Vaccine 18:1606–1612.PubMedCrossRefGoogle Scholar
  24. Mazzoni, A. and Segal, D. M. 2004. Controlling the Toll road to dendritic cell polarization. J Leukoc Biol 75:721–730.PubMedCrossRefGoogle Scholar
  25. Miller, R. A. 1991. Aging and immune function, Int Rev Cytol 124:187–215. Abstract | View Record in Scopus | Cited By in Scopus (148)Google Scholar
  26. Miller, R. A. 1996. The aging immune system: primer and prospectus. Science 273:70–74.PubMedCrossRefGoogle Scholar
  27. Narbutt, J., Lesiak, A., Zak-Prelich, M., Wozniacka, A., Sysa-Jedrzejowska, A., Tybura, M., Robak, T. and Smolewski, P. 2004. The distribution of peripheral blood dendritic cells assayed by a new panel of anti-BDCA monoclonal antibodies in healthy representatives of the polish population. Cell Mol Biol Lett 9:497–509.PubMedGoogle Scholar
  28. Perez-Cabezas, B., Naranjo-Gomez, M., Fernandez, M. A., Grifols, J. R., Pujol-Borrell, R. and Borras, F. E. 2007. Reduced numbers of plasmacytoid dendritic cells in aged blood donors. Exp Gerontol 42:1033–1038.PubMedCrossRefGoogle Scholar
  29. Pietschmann, P., Hahn, P., Kudlacek, S., Thomas, R. and Peterlik, M. 2000. Surface markers and transendothelial migration of dendritic cells from elderly subjects. Exp Gerontol 35:213–224.PubMedCrossRefGoogle Scholar
  30. Saurwein-Teissl, M., Schonitzer, D. and Grubeck-Loebenstein, B. 1998. Dendritic cell responsiveness to stimulation with influenza vaccine is unimpaired in old age. Exp Gerontol 33:625–631.PubMedCrossRefGoogle Scholar
  31. Sharma, M. D., Baban, B., Chandler, P., Hou, D. Y., Singh, N., Yagita, H., Azuma, M., Blazar, B. R., Mellor, A. L. and Munn, D. H. 2007. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest 117:2570–2582.PubMedCrossRefGoogle Scholar
  32. Sharma, S., Dominguez, A. L., Hoelzinger, D. B. and Lustgarten, J. 2008. CpG-ODN but not other TLR-ligands restore the antitumor responses in old mice: the implications for vaccinations in the aged. Cancer Immunol Immunother 57:549–561.PubMedCrossRefGoogle Scholar
  33. Sharma, S., Dominguez, A. L. and Lustgarten, J. 2006a. Aging affect the anti-tumor potential of dendritic cell vaccination, but it can be overcome by co-stimulation with anti-OX40 or anti-4-1BB. Exp Gerontol 41:78–84.PubMedCrossRefGoogle Scholar
  34. Sharma, S., Dominguez, A. L. and Lustgarten, J. 2006b. High accumulation of T regulatory cells prevents the activation of immune responses in aged animals. J Immunol 177:8348–8355.PubMedGoogle Scholar
  35. Shi, M., Bi, X., Xu, S., He, Y., Guo, X. and Xiang, J. 2005. Increased susceptibility of tumorigenicity and decreased anti-tumor effect of DC vaccination in aged mice are potentially associated with increased number of NK1.1+CD3+ NKT cells. Exp Oncol 27:125–129.PubMedGoogle Scholar
  36. Shodell, M. and Siegal, F. P. 2002. Circulating, interferon-producing plasmacytoid dendritic cells decline during human ageing. Scand J Immunol 56:518–521.PubMedCrossRefGoogle Scholar
  37. 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
  38. Sprecher, E., Becker, Y., Kraal, G., Hall, E., Harrison, D. and Shultz, L. D. 1990. Effect of aging on epidermal dendritic cell populations in C57BL/6 J mice. J Invest Dermatol 94:247–253.PubMedCrossRefGoogle Scholar
  39. Steger, M. M., Maczek, C. and Grubeck-Loebenstein, B. 1996. Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals. Clin Exp Immunol 105:544–550.PubMedCrossRefGoogle Scholar
  40. Teig, N., Moses, D., Gieseler, S. and Schauer, U. 2002. Age-related changes in human blood dendritic cell subpopulations. Scand J Immunol 55:453–457.PubMedCrossRefGoogle Scholar
  41. Tesar, B. M., Walker, W. E., Unternaehrer, J., Joshi, N. S., Chandele, A., Haynes, L., Kaech, S. and Goldstein, D. R. 2006. Murine [corrected] myeloid dendritic cell-dependent toll-like receptor immunity is preserved with aging. Aging Cell 5:473–486.PubMedCrossRefGoogle Scholar
  42. van Kooyk, Y. and Geijtenbeek, T. B. 2002. A novel adhesion pathway that regulates dendritic cell trafficking and T cell interactions. Immunol Rev 186:47–56.PubMedCrossRefGoogle Scholar
  43. Vuckovic, S., Gardiner, D., Field, K., Chapman, G. V., Khalil, D., Gill, D., Marlton, P., Taylor, K., Wright, S., Pinzon-Charry, A., Pyke, C. M., Rodwell, R., Hockey, R. L., Gleeson, M., Tepes, S., True, D., Cotterill, A. and Hart, D. N. 2004. Monitoring dendritic cells in clinical practice using a new whole blood single-platform TruCOUNT assay. J Immunol Methods 284:73–87.PubMedCrossRefGoogle Scholar
  44. Watts, C., Zaru, R., Prescott, A. R., Wallin, R. P. and West, M. A. 2007. Proximal effects of Toll-like receptor activation in dendritic cells. Curr Opin Immunol 19:73–78.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.University of MichiganMichiganUSA

Personalised recommendations