CD4⁺CD25^high regulatory cells in peripheral blood of NSCLC patients

Abstract

The proportion and changes of CD4⁺CD25^high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral blood was collected from 61 patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with the flow cytometry for lymphocyte subsets (CD3⁺, CD4⁺ and CD8⁺) and CD4⁺CD25^high Tr cells. The results showed that the proportion of CD4⁺CD25^high Tr cells in NSCLC group was significantly higher than in control group [(4.36±2.07) % vs (2.04±1.03) %, P<0.01]. The proportion of CD4⁺CD25^high Tr cells in late stage was higher than that in early stage [stages: + II (2.26±0.6) %; stage III (3.28±1.38) %; stage IV (6.06±4.08) %] (P<0.05). Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher proportion of CD4⁺CD25^high Tr cells in peripheral blood was worse (P=0.0026). In conclusion, the relative increase in CD4⁺CD25^high Tr cells in peripheral blood may be related to immunosuppression and tumor progression in patients with NSCLC. This finding suggests that CD4⁺CD25^+high Tr cells in peripheral blood of NSCLC may be positive for prognosis analysis. The use of depletion of the CD4⁺CD25^high Tr cell therapy to treat NSCLC patients may be an effective strategy.

Keywords

non-small cell lung cancer / T subsets / CD4⁺CD25^high regulatory T cell / flow cytometry / survival analysis

References

[1] SakaguchiS., SakaguchiN., AsanoM., et al.. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol, 1995, 155: 1151-1164

[2] DieckmannD., PlottnerH., BerchtoldS., et al.. Ex vivo isolation and characterization of CD4⁺CD25⁺T cells with regulatory properties from human blood. J Exp Med, 2001, 193: 1303-1310

[3] AsanoM., TodaM., SakaguchiN., et al.. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med, 1996, 184: 387-396

[4] ShevachE. M.. Certified professionals: CD4⁺CD25⁺ suppressor T cells. J Exp Med, 2001, 193: F41-F46

[5] PiccirilloC. A., ShevachE. M.. Cutting edge: control of CD8⁺ T cell activation by CD4⁺CD25⁺ immunoregulatory cells. J Immunol, 2001, 167: 1137-1140

[6] Baecher-AllanC., BrownJ. A., GordonJ., et al.. CD4⁺CD25^high regulatory cells in human peripheral blood. J Immunol, 2001, 167: 1245-1253

[7] SasadaT., KimuraM., YoshidaY., et al.. CD4⁺CD25⁺ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer, 2003, 98: 1089-1098

[8] RosenbergS. A.. Progress in human tumor immunology and immunotherapy. Nature, 2001, 411: 380-384

[9] TanakaH., TanakaJ., KjaergaardJ., et al.. Depletion of CD4⁺CD25⁺ regulatory cells augments the generation of specific immune T cells in tumor-draining lymph nodes. J Immunother, 2002, 25: 207-217

[10] DiederichsenA. C., HjelmborgJ. B., ChristensenP. B., et al.. Prognostic value of the CD4⁺/CD8⁺ ratio of the tumor infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumor cells. Cancer Immunol Immunother, 2003, 52: 423-428

[11] NiuH. Q., DongZ., DongF. Y., et al.. Experimental and clinical research of dendritic cell and syngeneic immunotherapy of brain glioma. Chinese-German J Clin Oncol, 2004, 3: 147-150

[12] NagaiH., HorikawaT., HaraI., et al.. In vivo elimination of CD25⁺ regulatory T cells leads to tumor rejection of B16F10 melanoma, when combined with interleukin-12 gene transfer. Exp Dermatol, 2004, 13: 613-620