Skip to main content

Advertisement

SpringerLink
Log in

Immunosenescence, suppression and tumour progression

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

Abstract

There are good arguments for suggesting that two seminal papers published 50 years ago can be taken as the beginning of modern tumour immunology. These papers by R. Baldwin, “Immunity to transplanted tumour: the effect of tumour extracts on the growth of homologous tumours in rats” and “Immunity to methylcholanthrene-induced tumours in inbred rats following atrophy and regression of the implanted tumours” (Br J Cancer 9:646–51 and 652–657, 1955) showed that once tumours are established, they and their products can be recognised by the adaptive immune system and rejected. However, the tumour normally co-evolves with immunity, like a parasite, rather than being suddenly introduced as in these, and many other, experimental models. Dynamics of this co-evolution are illustrated by findings that inflammation enhances tumorigenicity, yet is important to enable T cells to respond properly to tumour antigen and exert anti-tumour effects. The important thing is to maintain the balance between effective anti-tumour immunity and tumour escape and/or stimulatory mechanisms. Tumours almost always co-exist with immune defence systems over extended periods and interact chronically with T cells. The effect of this is potentially similar to other situations of chronic antigenic stress, particularly lifelong persistent virus infection, most strikingly, CMV infection. The questions briefly explored in this symposium paper are what happens when T lymphocyte clones are chronically stimulated by antigen which is not or cannot be eliminated? What are the similarities and differences between chronic antigenic stimulation by tumour antigen versus CMV antigen? What can we learn in one system which may illuminate the other?

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
Fig. 2

Similar content being viewed by others

References

  1. Pawelec G (2003) T cell immunosenescence. In: Kaul SC, Wadhwa R (eds) Aging of cells in and outside the body, chapter 6. Biology of aging and its modulation, vol 1, series editor Suresh Rattan. Kluwer, Dordrecht, pp 85–100

  2. Hooijberg E, Ruizendaal JJ, Snijders PJ, Kueter EW, Walboomers JM, Spits H (2000) Immortalization of human CD8+ T cell clones by ectopic expression of telomerase reverse transcriptase. J Immunol 165:4239–4245

    PubMed  CAS  Google Scholar 

  3. Migliaccio M, Amacker M, Just T, Reichenbach P, Valmori D, Cerottini JC, Romero P, Nabholz M (2000) Ectopic human telomerase catalytic subunit expression maintains telomere length but is not sufficient for CD8+ T lymphocyte immortalization. J Immunol 165:4978–4984

    PubMed  CAS  Google Scholar 

  4. Welsh RM, McNally JM (1999) Immune deficiency, immune silencing, and clonal exhaustion of T cell responses during viral infections. Curr Opin Microbiol 2:382–387

    Article  PubMed  CAS  Google Scholar 

  5. Kiessling R, Pawelec G, Welsh RM, Barry JD, Ferrone S (2000) Have tumor cells learnt from microorganisms how to fool the immune system? Escape from immune surveillance of tumors and microorganisms: emerging mechanisms and shared strategies. Mol Med Today 6:344–346

    Article  PubMed  CAS  Google Scholar 

  6. Soares MV, Maini MK, Beverley PC, Salmon M, Akbar AN (2000) Regulation of apoptosis and replicative senescence in CD8+ T cells from patients with viral infections. Biochem Soc Trans 28:255–258

    PubMed  CAS  Google Scholar 

  7. Pawelec G, Mariani E, Solana R, Forsey R, Larbi A, Neri S, Dela Rosa O, Barnett Y, Tolson J, Fülöp T (2005) Human T cell clones in long-term culture as models for the impact of chronic antigenic stress in ageing. In: Conn M (ed) Handbook of models of human aging. Elsevier, Amsterdam (in press)

  8. Pawelec G, Rehbein A, Hähnel K, Adibzadeh M, Wagner W, Engel A (2000) In vitro senescence models for human T lymphocytes. Vaccine 18:1666–1674

    Article  PubMed  CAS  Google Scholar 

  9. Pawelec G, Rehbein A, Haehnel K, Merl A, Adibzadeh M (1997) Human T cell clones in long-term culture as a model of immunosenescence. Immunol Rev 160:31–42

    Article  PubMed  CAS  Google Scholar 

  10. Pawelec G, Schneider EM, Wernet P (1986) Acquisition of suppressive activity and natural killer-like cytotoxicity by human alloproliferative “helper” T cell clones. J Immunol 136:402–411

    PubMed  CAS  Google Scholar 

  11. Pawelec G, Fernandez N, Brocker T, Schneider EM, Festenstein H, Wernet P (1988) DY determinants, possibly associated with novel class II molecules, stimulate autoreactive CD4+ T cells with suppressive activity. J Exp Med 167:243–261

    Article  PubMed  CAS  Google Scholar 

  12. Hyland P, Barnett C, Pawelec G, Barnett Y (2001) Increased levels of oxidative DNA damage and alterations in the levels of the mitotic inhibitors p16INK4a/CDKN2a, p21WAF1/CIP1/SDI1, p27KIP1 leads to T cell replicative senescence in vitro. Mech Ageing Dev 122:1151–1167

    Article  PubMed  CAS  Google Scholar 

  13. Posnett DN, Sinha R, Kabak S, Russo C (1994) Clonal populations of T cells in normal elderly humans: the T cell equivalent to “benign monoclonal gammopathy”. J Exp Med 179:609–618

    Article  PubMed  CAS  Google Scholar 

  14. Looney RJ, Falsey A, Campbell D, Torres A, Kolassa J, Brower C, McCann R, Menegus M, McCormick K, Frampton M, Hall W, Abraham GN (1999) Role of cytomegalovirus in the T cell changes seen in elderly individuals. Clin Immunol 90:213–219

    Article  PubMed  CAS  Google Scholar 

  15. Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A (2005) Human immunosenescence. Is it infectious? Immunol Rev 205:257–268

    Article  PubMed  CAS  Google Scholar 

  16. Wills MR, Okecha G, Weekes MP, Gandhi MK, Sissons PJ, Carmichael AJ (2002) Identification of naive or antigen-experienced human CD8+ T cells by expression of costimulation and chemokine receptors: analysis of the human cytomegalovirus-specific CD8+ T cell response. J Immunol 168:5455–5464

    PubMed  CAS  Google Scholar 

  17. Elbou Ould MA, Luton D, Yadini M, Pedron B, Aujard Y, Jacqz-Aigrain E, Jacquemard F, Sterkers G (2004) Cellular immune response of fetuses to cytomegalovirus. Pediatr Res 55:280–286

    Article  PubMed  CAS  Google Scholar 

  18. Wikby A, Ferguson F, Forsey R, Thompson J, Strindhall J, Löfgren S, Nilsson B-O, Ernerudh J, Pawelec G, Johansson B (2005) An immune risk phenotype, cognitive impairment and survival in very late life: the impact of allostatic load in Swedish Octo- and Nonagenarian humans. J Gerontol B 60:556–565

    Google Scholar 

  19. Ouyang Q, Wagner WM, Zheng W, Wikby A, Remarque EJ, Pawelec G (2004) Dysfunctional CMV-specific CD8+ T cells accumulate in the elderly. Exp Gerontol 39:607–613

    Article  PubMed  CAS  Google Scholar 

  20. Voehringer D, Koschella M, Pircher H (2002) Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectin-like receptor G1 (KLRG1). Blood 100:3698–3702

    Article  PubMed  CAS  Google Scholar 

  21. Ibegbu CC, Xu YX, Harris W, Maggio D, Miller JD, Kourtis AP (2005) Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T lymphocytes during active, latent, and resolved infection and its relation with CD57. J Immunol 174:6088–6094

    PubMed  CAS  Google Scholar 

  22. Kaesberg PR, Ershler WB (1989) The change in tumor aggressiveness with age: lessons from experimental animals. Semin Oncol 16:28–33

    PubMed  CAS  Google Scholar 

  23. Provinciali M, Smorlesi A (2005) Immunoprevention and immunotherapy of cancer in ageing. Cancer Immunol Immunother 54:93–106

    Article  PubMed  Google Scholar 

  24. Effros RB (2004) Replicative senescence of CD8 T cells: potential effects on cancer immune surveillance and immunotherapy. Cancer Immunol Immunother 53:925–933

    Article  PubMed  Google Scholar 

  25. thor Straten P, Kirkin AF, Siim E, Dahlstrom K, Drzewiecki KT, Seremet T, Zeuthen J, Becker JC, Guldberg P (2000) Tumor infiltrating lymphocytes in melanoma comprise high numbers of T-cell clonotypes that are lost during in vitro culture. Clin Immunol 96:94–99

    Article  PubMed  CAS  Google Scholar 

  26. Walter S, Bioley G, Bühring H-J, Koch S, Wernet D, Zippelius A, Pawelec G, Romero P, Stevanović S, Rammensee H-G, Gouttefangeas C (2005) High frequencies of functionally impaired cytokeratin 18-specific CD8+ T cells in healthy HLA-A2+ donors. Eur J Immunol 35:2876–2885

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The work mentioned here was most recently supported by the Deutsche Forschungsgemeinschaft through SFB 685 “Immunotherapy: from molecular basis to clinical application” and the EU through projects 6FP 503306 “European Network for the Identification and Validation of Antigens and Biomarkers in Cancer and their Application in Tumour Immunology, ENACT”; QLRT-2001-00668 “Outcome and impact of specific treatment in European research on melanoma” and QLK6-CT-2002-02283 “T cells in ageing, T-CIA”.

Author information

Authors and Affiliations

  1. Center for Medical Research and Department of Immunology, University of Tübingen, Tübingen, Germany

    G. Pawelec, S. Koch, H. Griesemann, A. Rehbein, K. Hähnel & C. Gouttefangeas

Authors
  1. G. Pawelec
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Griesemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Rehbein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Hähnel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Gouttefangeas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Pawelec.

Additional information

This article is a symposium paper from the “Robert Baldwin Symposium: 50 years of Cancer Immunotherapy”, held in Nottingham, Great Britain, on 30 June 2005.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pawelec, G., Koch, S., Griesemann, H. et al. Immunosenescence, suppression and tumour progression. Cancer Immunol Immunother 55, 981–986 (2006). https://doi.org/10.1007/s00262-005-0109-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-005-0109-3

Keywords

Search

Navigation