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

Lung Cancer. 2012 Aug;77(2):306-11. doi: 10.1016/j.lungcan.2012.04.011. Epub 2012 May 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / metabolism*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Case-Control Studies
  • Female
  • Gene Expression
  • Humans
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • CTLA-4 Antigen