Skip to main content

Advertisement

Log in

CD8+CD28− cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Aim To evaluate the CD8+CD28− and CD4+CD25+ regulatory T (Treg) cells in addition to other some lymphocyte subgroups in peripheral blood of advanced stage lung cancer patients. Methods The study group (n = 28) comprised chemotherapy and radiotherapy naïve patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The control group (n = 22) consisted of age- and sex-matched healthy volunteers. Flow cytometry was used to count T cells, natural killer (NK) cells and CD4+CD25 Treg cells, and for CD8+ T cell subgroup analysis. Flow cytometry was performed and annexin V binding was used for apoptotic cell evaluation. Results In patient group, the percentage of CD8+CD28− cells among lymphocytes was elevated, and there was also an increase in the CD28−/CD28+ cell ratio among CD8 lymphocyte population. The distribution of CD8 cells was different in lung cancer patients when compared with the control group. The absolute count of CD4+CD25bright cells and the percentages of these cells among total lymphocytes were higher in the patient group. The Annexin V(+) cell percentages among CD8+CD28− and CD8+CD28+ lymphocytes were higher in the patient group than in the control group. No differences were found between the NSCLC and SCLC patients with respect to the hematological parameters and the distribution of lymphocyte subgroups. In NSCLC patients, the percentage of CD8+CD28− cells among the lymphocyte population was higher in patients with stage IV than those with stage III. Conclusion These findings may reflect the possibility of tumor-induced immunosuppression and they should be complemented with further studies.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Sakaguchi S. Regulatory T cells: key controllers of immunologic self-tolerance. Cell. 2000;101:455–8. doi:10.1016/S0092-8674(00)80856-9.

    Article  CAS  PubMed  Google Scholar 

  2. Yi H, Zhen Y, Jiang L, Zheng J, Zhao Y. The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T cells. Cell Mol Immunol. 2006;3:189–95.

    CAS  PubMed  Google Scholar 

  3. Zhang L, Zhao Y. The regulation of Foxp3 expression in regulatory CD4(+)CD25(+)T cells: multiple pathways on the road. J Cell Physiol. 2007;211:590–7. doi:10.1002/jcp.21001.

    Article  CAS  PubMed  Google Scholar 

  4. Maggi E, Cosmi L, Liotta F, Romagnani P, Romagnani S, Annunziato F. Thymic regulatory T cells. Autoimmun Rev. 2005;4:579–86. doi:10.1016/j.autrev.2005.04.010.

    Article  CAS  PubMed  Google Scholar 

  5. Sakaguchi S. The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J Clin Invest. 2003;112:1310–2.

    CAS  PubMed  Google Scholar 

  6. Taams LS, Akbar AN. Peripheral generation and function of CD4+CD25+ regulatory T cells. Curr Top Microbiol Immunol. 2005;293:115–31. doi:10.1007/3-540-27702-1_6.

    Article  CAS  PubMed  Google Scholar 

  7. Valencia X, Yarboro C, Illei G, Lipsky PE. Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol. 2007;178:2579–88.

    CAS  PubMed  Google Scholar 

  8. Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL. CD4(+)CD25(+) immunoregulatory T cells: new therapeutics for graft-versus-host disease. J Exp Med. 2002;196:401–6. doi:10.1084/jem.20020090.

    Article  CAS  PubMed  Google Scholar 

  9. Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 2002;196:389–99. doi:10.1084/jem.20020399.

    Article  CAS  PubMed  Google Scholar 

  10. Terabe M, Berzofsky JA. Immunoregulatory T cells in tumor immunity. Curr Opin Immunol. 2004;16:157–62. doi:10.1016/j.coi.2004.01.010.

    Article  CAS  PubMed  Google Scholar 

  11. Wei WZ, Morris GP, Kong YC. Anti-tumor immunity and autoimmunity: a balancing act of regulatory T cells. Cancer Immunol Immunother. 2004;53:73–8. doi:10.1007/s00262-003-0444-1.

    Article  CAS  PubMed  Google Scholar 

  12. Kono K, Kawaida H, Takahashi A, Sugai H, Mimura K, Miyagawa N, et al. CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother. 2006;55:1064–71. doi:10.1007/s00262-005-0092-8.

    Article  CAS  PubMed  Google Scholar 

  13. Chikamatsu K, Sakakura K, Whiteside TL, Furuya N. Relationships between regulatory T cells and CD8+ effector populations in patients with squamous cell carcinoma of the head and neck. Head Neck. 2007;29:120–7. doi:10.1002/hed.20490.

    Article  PubMed  Google Scholar 

  14. Lau KM, Cheng SH, Lo KW, Lee SA, Woo JK, van Hasselt CA, et al. Increase in circulating Foxp3+CD4+CD25(high) regulatory T cells in nasopharyngeal carcinoma patients. Br J Cancer. 2007;96:617–22. doi:10.1038/sj.bjc.6603580.

    Article  CAS  PubMed  Google Scholar 

  15. Peng QQ, Li SP, Xu L, Li JQ. Clinical significance of the proportion of CD4+CD25+ regulatory T cells in peripheral blood of hepatocellular carcinoma patients: a report of 117 cases. Ai Zheng. 2007;26:748–51.

    PubMed  Google Scholar 

  16. Najafian N, Chitnis T, Salama AD, Zhu B, Benou C, Yuan X, et al. Regulatory functions of CD8+CD28− T cells in an autoimmune disease model. J Clin Invest. 2003;112:1037–48.

    CAS  PubMed  Google Scholar 

  17. Filaci G, Fravega M, Negrini S, Procopio F, Fenoglio D, Rizzi M, et al. Nonantigen specific CD8+ T suppressor lymphocytes originate from CD8+CD28− T cells and inhibit both T-cell proliferation and CTL function. Hum Immunol. 2004;65:142–56. doi:10.1016/j.humimm.2003.12.001.

    Article  CAS  PubMed  Google Scholar 

  18. Filaci G, Fenoglio D, Fravega M, Ansaldo G, Borgonovo G, Traverso P, et al. CD8+ CD28− T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J Immunol. 2007;179:4323–34.

    CAS  PubMed  Google Scholar 

  19. Tsukishiro T, Donnenberg AD, Whiteside TL. Rapid turnover of the CD8(+)CD28(−) T-cell subset of effector cells in the circulation of patients with head and neck cancer. Cancer Immunol Immunother. 2003;52:599–607. doi:10.1007/s00262-003-0395-6.

    Article  PubMed  Google Scholar 

  20. Meloni F, Morosini M, Solari N, Passadore I, Nascimbene C, Novo M, et al. Foxp3 expressing CD4+ CD25+ and CD8+ CD28− T regulatory cells in the peripheral blood of patients with lung cancer and pleural mesothelioma. Hum Immunol. 2006;67:1–12. doi:10.1016/j.humimm.2005.11.005.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bülent Karagöz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karagöz, B., Bilgi, O., Gümüs, M. et al. CD8+CD28− cells and CD4+CD25+ regulatory T cells in the peripheral blood of advanced stage lung cancer patients. Med Oncol 27, 29–33 (2010). https://doi.org/10.1007/s12032-008-9165-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-008-9165-9

Keywords

Navigation