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

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2012-08, Vol.77 (2), p.306-311
• Main Authors: Erfani, Nasrollah, Mehrabadi, Shayesteh Mofakhami, Ghayumi, Mohammad Ali, Haghshenas, Mohammad Reza, Mojtahedi, Zahra, Ghaderi, Abbas, Amani, Davar
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Case-Control Studies; CTLA-4; CTLA-4 Antigen - genetics; CTLA-4 Antigen - metabolism; Female; FoxP3; Gene Expression; Hematology, Oncology and Palliative Medicine; Humans; Lung cancer; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Male; Medical sciences; Middle Aged; Neoplasm Staging; Non-small cell lung cancer; Pneumology; Pulmonary/Respiratory; Regulatory T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tumor immunology; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2012.04.011

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.