Increase of regulatory T cells in metastatic stage and CTLA-4 over expression in lymphocytes of patients with non-small cell lung cancer (NSCLC)

We hypothesized that the increased percentages of Regulatory T (Treg) cells, as well as over expression of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) by lymphocyte subsets might be associated with lung cancer. Accordingly, peripheral blood of 23 new cases with non-small cell lung cancer (NSCLC) and 16 healthy volunteers were investigated, by follow cytometry, for the prevalence of CD4+CD25+FoxP3+Treg cells as well as surface (sur-) and intracellular (In-) expression of CTLA-4 by the main lymphocyte subsets (CD4+, CD8+ and CD19+). Results indicated that NSCLC patients had an increased percentage of Treg cells than controls (7.9 +/- 4.1 versus 3.8 +/- 1.8, P = 0.001). The proportion of Treg cells was observed to be increased by stage increase in patients (stage II = 5.2 +/- 2.4, stage III = 7.9 +/- 4.4, stage IV=12.0 +/- 2.2), and also significantly higher in metastatic than non-metastatic stages (12.0 +/- 2.2 versus 6.8 +/- 3.9, P=0.023). Increase of SurCTLA-4- as well as InCTLA-4-expressing lymphocytes in patients were observed in nearly all investigated subsets, but significant differences between patients and controls were observed about InCTLA-4+CD4+ lymphocytes (8.6 +/- 7.1 and 3.8 +/- 5.3 respectively, P = 0.006) as well as SurCTLA-4+CD8+ lymphocytes (0.3 +/- 0.2 and 0.2 +/- 0.1 respectively, P = 0.047). In conclusion, the results suggest that immunotherapy regimen targeting CTLA-4 and Treg cells might be beneficial in lung cancer patients. (C) 2012 Elsevier Ireland Ltd. All rights reserved.