Skip to main content

Advertisement

SpringerLink
Log in

Immunosenescence and cancer vaccines

  • Symposium in Writing
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Experimental and clinical data demonstrate that ageing is associated with the gradual deterioration of the immune system, generally referred to as immunosenescence. Age-related immune dysfunction may have an impact not only on the incidence of cancer, but also on the preventive and therapeutic approaches, which are based on immune system activation. Over the last few years the use of immunological measures to prevent cancer in experimental mouse models involving preimmunisation with new vaccines against even a poor or apparently non-immunogenic tumour has yielded worse outcomes in older age than in young adults. Different mechanisms, which may be due to age-related numerical or functional dysfunction of immune cells and/or to tumour microenvironmental changes, could be responsible for this defect. This review summarises the impact of immunosenescence on the effectiveness of cancer vaccines, knowledge of cancer immunisation in old age and the potential mechanisms implicated in the poorer effectiveness of anticancer immune-based approaches in advanced age. Several approaches to, and possibilities of correcting the low effectiveness of immunisation procedures in old age are described.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Argentati K, Re F, Donnini A, Tucci MG, Franceschi C, Bartozzi B, Bernardini G, Provinciali M (2002) Numerical and functional alterations of circulating γδ T lymphocytes in aged people and centenarians. J Leukoc Biol 72:65

    PubMed  CAS  Google Scholar 

  2. Bluestone JA, Abbas AK (2003) Natural versus adaptive regulatory T-cells. Nat Rev Immunol 3:253

    Article  PubMed  CAS  Google Scholar 

  3. Bunt SK, Yang L, Sinha P, Clements VK, Leips J, Ostrand-Rosenberg S (2007) Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression. Cancer Res 67:10019

    Article  PubMed  CAS  Google Scholar 

  4. Carter L, Fouser LA, Jussif J, Fitz L, Deng B, Wood CR et al (2002) PD-1:PD-L inhibitory pathway affects both CD4+ and CD8+ T cells and is overcome by IL-2. Eur J Immunol 32:634

    Article  PubMed  CAS  Google Scholar 

  5. Casetti R, Martino A (2008) The plasticity of γδ T cells: innate immunity, antigen presentation and new immunotherapy. Cell Mol Immunol 5:161

    Article  PubMed  CAS  Google Scholar 

  6. Cavallo F, Signorelli P, Giovarelli M, Musiani P, Modesti A, Brunda MJ, Colombo MP, Forni G (1997) Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12 (IL-12) or other cytokines compared with exogenous IL-12. J Natl Cancer Inst 89:1049

    Article  PubMed  CAS  Google Scholar 

  7. Donnini A, Argentati K, Mancini R, Smorlesi A, Bartozzi B, Bernardini G, Provinciali M (2002) Phenotype, antigen-presenting capacity, and migration of antigen-presenting cells in young and old age. Exp Gerontol 37:1097

    Article  PubMed  CAS  Google Scholar 

  8. Donnini A, Re F, Orlando F, Provinciali M (2007) Intrinsic and microenvironmental defects are involved in the age-related changes of Lin−c-kit+ hematopoietic progenitor cells. Rejuvenation Res 10:459

    Article  PubMed  CAS  Google Scholar 

  9. Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, Casti A, Franceschi C, Passeri M, Sansoni P (2000) Shortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging. Blood 95:2860

    PubMed  CAS  Google Scholar 

  10. Ferrarini M, Ferrero E, Dagna L, Poggi A, Zocchi MR (2002) Human γδ T cells: a nonreduntant system in the immune-surveillance against cancer. Trends Immunol 23:14

    Article  PubMed  CAS  Google Scholar 

  11. Finn OJ (2003) Cancer vaccines: between the idea and the reality. Nat Immunol 3:630

    Article  CAS  Google Scholar 

  12. Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65:S173

    Article  PubMed  Google Scholar 

  13. Francipane MG, Perez Alea M, Lombardo Y, Todaro M, Medema JP, Stassi G (2008) Crucial role of interleukin-4 in the survival of colon cancer stem cells. Cancer Res 68:4022

    Article  PubMed  CAS  Google Scholar 

  14. Frick B, Schroecksnadel K, Neurauter G, Leblhuber F, Fuchs D (2004) Increasing production of homocysteine and neopterin and degradation of tryptophan with older age. Clin Biochem 37:684

    Article  PubMed  CAS  Google Scholar 

  15. Fukaura H, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Hafler DA (1996) Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factorbeta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. J Clin Invest 98:70

    Article  PubMed  CAS  Google Scholar 

  16. Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP, Basso G, Brombacher F, Borrrello I, Zanovello P, Bicciato S, Bronte V (2006) Tumors induce a subset of inflammatory monocytes with immunosoppressive activity on CD8+ T cells. J Clin Invest 116:2777

    Article  PubMed  CAS  Google Scholar 

  17. Goodwin JS, Messner RP (1979) Sensitivity of lymphocytes to prostaglandin E2 increases in subjects over age 70. J Clin Invest 64:434

    Article  PubMed  CAS  Google Scholar 

  18. Gravekamp C (2007) Cancer vaccines in old age. Exp Gerontol 42:441

    Article  PubMed  CAS  Google Scholar 

  19. Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family revisited. Annu Rev Immunol 23:515

    Article  PubMed  CAS  Google Scholar 

  20. Gregg R, Smith CM, Clark FJ, Dunnion D, Khan N, Chakravertry R, Nayak L, Moss PA (2005) The number of human peripheral blood CD4+CD25high regulatory T cells increases with age. Clin Exp Immunol 140:540

    Article  PubMed  CAS  Google Scholar 

  21. Grizzle WE, Xu X, Zhang S, Stockard CR, Liu C, Yu S, Wang J, Mountz JD, Zhang HG (2007) Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice. Mech Ageing Dev 128:672

    Article  PubMed  CAS  Google Scholar 

  22. Groux H, O’Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389:737

    Article  PubMed  CAS  Google Scholar 

  23. Haugen E, Li-Ming G, Isic A, Skommevik T, Fu M (2008) Increased interleukin-6 but not tumour factor necrosis-alpha predicts mortality in the population of elderly heart failure patients. Exp Clin Cardiol 13:19

    PubMed  CAS  Google Scholar 

  24. Henson SM, Macaulay R, Kiani-Alikhan S, Akbar AN (2008) The use of the inhibitory receptors for modulating the immune responses. Curr Pharm Des 14:2643

    Article  PubMed  CAS  Google Scholar 

  25. Jones E, Dahm-Vicker M, Simon AK, Green A, Powrie F, Cerundolo V, Gallimore A (2002) Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun 2:1

    PubMed  Google Scholar 

  26. Kabelitz D, Wesch D, He W (2007) Perspectives of γδ T cells in tumor immunology. Cancer Res 67:5

    Article  PubMed  CAS  Google Scholar 

  27. Lages CS, Suffia I, Velilla PA, Huang B, Warshaw G, Hildeman DA, Belkaid Y, Chougnet C (2008) Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol 181:1835

    PubMed  CAS  Google Scholar 

  28. Lustgarten J, Dominguez AL, Thoman M (2004) Aged mice develop protective antitumor responses with appropriate costimulation. J Immunol 173:4510

    PubMed  CAS  Google Scholar 

  29. Mak TW, Ferrick DA (1998) The γδ T cell bridge: linking innate and acquired immunity. Nat Med 4:764

    Article  PubMed  CAS  Google Scholar 

  30. Massari I, Donnini A, Argentati K, Straino S, Mangoni A, Gaetano C, Viticchi C, Capogrossi MC, Provinciali M (2002) Age-dependent effects of repeated immunization with a first generation adenovirus vector on the immune response and transgene expression in young and old rats. Exp Gerontol 37:823

    Article  PubMed  CAS  Google Scholar 

  31. Murakami M, Sakamoto A, Bender J, Kappler J, Marrack P (2002) CD25+CD4+ T cells contribute to the control of memory CD8+ T cells. PNAS 99:8832

    Article  PubMed  CAS  Google Scholar 

  32. Mumm JB, Oft M (2008) Cytokine-based transformation of immune surveillance into tumor-promoting inflammation. Oncogene 27:5913

    Article  PubMed  CAS  Google Scholar 

  33. Nishioka T, Shimizu J, Iida R, Yamazaki S, Sakaguchi S (2006) CD4+CD25+Foxp3+ T cells and CD4+CD25−Foxp3* T cells in aged mice. J Immunol 176:6586

    PubMed  CAS  Google Scholar 

  34. Oshikawa K, Shi F, Rakhmilevich AL, Sondel PM, Mahvi DM, Yang NS (1999) Synergistic inhibition of tumor growth in a murine mammary adenocarcinoma model by combinational gene therapy using IL-12, pro-IL 18, and IL-1 beta converting enzyme cDNA. Proc Natl Acad Sci 96:13351

    Article  PubMed  CAS  Google Scholar 

  35. Pawelec G, Solana R (1997) Immunosenescence. Trends Immunol 11:514

    Google Scholar 

  36. Pertovaara M, Raitala A, Lehtimaki T, Karhunen PJ, Oja SS, Jylha M, Hervonen A, Hurme M (2006) Indoleamine 2,3-dioxygenase activity in nonagenarians is markedly increased and predicts mortality. Mech Ageing Dev 127:497

    PubMed  CAS  Google Scholar 

  37. Provinciali M, Fabris N, Pieri C (1990) Improvement of natural killer cell activity by in vitro active lipids (AL 721) administration in old mice. Mech Ageing Dev 52:245

    Article  PubMed  CAS  Google Scholar 

  38. Provinciali M, Argentati K, Tibaldi A (2000) Efficacy of cancer gene therapy in aging: adenocarcinoma cells engineered to release IL-2 are rejected but do not induce tumor specific immune memory in old mice. Gene Ther 7:624

    Article  PubMed  CAS  Google Scholar 

  39. Provinciali M, Smorlesi A, Donnini A, Bartozzi B, Amici A (2003) Low effectiveness of DNA vaccination against HER-2/neu in ageing. Vaccine 21:843

    Article  PubMed  CAS  Google Scholar 

  40. Provinciali M, Smorlesi A (2005) Immunoprevention and immunotherapy of cancer in aging. Cancer Immunol Immunother 54:93

    Article  PubMed  Google Scholar 

  41. Provinciali M, Donnini A, Smorlesi A, Gatti C (2008) Breast cancer and immunosenescence. In: Fulop T, Franceschi C, Hirokawa K, Pawelec G (eds) Immunosenescence handbook. Springer, Berlin (in press)

  42. Quaglino E, Iezzi M, Mastini C, Amici A, Pericle F, Di Carlo E, Pupa S, De Giovanni C, Spadaro M, Curcio C, Lollini PL, Musini P, Forni G, Cavallo F (2004) Electroporated DNA vaccine clears away multifocal mammari carcinomas in Her-2/neu transgenic mice. Cancer Res 64:2858

    Article  PubMed  CAS  Google Scholar 

  43. Re F, Poccia F, Donnini A, Bartozzi B, Bernardini G, Provinciali M (2005) Skewed representation of functionally distinct populations of Vγ9 Vδ2 T lymphocytes in aging. Exp Gerontol 40:59

    Article  PubMed  CAS  Google Scholar 

  44. Sansone P, Storci G, Tavolati S, Guarnieri T, Giovannini C, Taffurelli M, Ceccarelli C, Santini D, Paterini P, Marcu KB, Chieco P, Bonafè M (2007) IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 117:3988

    Article  PubMed  CAS  Google Scholar 

  45. Seth R-N (2006) Why cancer and inflammation? Yale J Biol Med 79:123

    Google Scholar 

  46. Sharma S, Dominguez A, Lustgarten J (2006) 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

    Article  PubMed  CAS  Google Scholar 

  47. Sharma S, Dominguez AL, Justgarten J (2006) High accumulation of T regulatory cells prevents the activation of immune responses in aged animals. J Immunol 177:8348

    PubMed  CAS  Google Scholar 

  48. Walker PR, Saas P, Dietrich P-Y (1997) Role of Fas ligand (CD95L) in immune escape. The tumor cell strikes back. J Immunol 158:4521

    PubMed  CAS  Google Scholar 

  49. Whiteside TL (2008) The tumor microenvironment and its role in promoting tumor growth. Oncogene 27:5904

    Article  PubMed  CAS  Google Scholar 

  50. Wicha MS, Liu S, Dontu G (2006) Cancer stem cells: an old idea-a paradigm shift. Cancer Res 66:1883

    Article  PubMed  CAS  Google Scholar 

  51. Zamanakou M, Germenis AE, Karanikas V (2007) Tumor immune escape mediated by indole amine 2,3-dioxygenase. Immunol Lett 111:69

    Article  PubMed  CAS  Google Scholar 

  52. Zou W (2006) Regulatory T cells, tumor immunity and immunotherapy. Nat Rev Immunol 6:295

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Tumour Immunology, INRCA Research Department, Via Birarelli 8, 60121, Ancona, Italy

    Mauro Provinciali

Authors
  1. Mauro Provinciali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mauro Provinciali.

Additional information

This article is part of the symposium in writing on “Impact of ageing on cancer immunity and immunotherapy”.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Provinciali, M. Immunosenescence and cancer vaccines. Cancer Immunol Immunother 58, 1959–1967 (2009). https://doi.org/10.1007/s00262-009-0665-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-009-0665-z

Keywords

Search

Navigation