Population alterations of l-arginase- and inducible nitric oxide synthase-expressed CD11b⁺/CD14⁻/CD15⁺/CD33⁺ myeloid-derived suppressor cells and CD8⁺ T lymphocytes in patients with advanced-stage non-small cell lung cancer

• Published in: Journal of cancer research and clinical oncology Vol. 136; no. 1; pp. 35 - 45
• Main Authors: Liu, Chien-Ying, Wang, Yu-Min, Wang, Chih-Liang, Feng, Po-Hao, Ko, How-Wen, Liu, Yun-Hen, Wu, Yi-Cheng, Chu, Yen, Chung, Fu-Tsai, Kuo, Chih-Hsi, Lee, Kang-Yun, Lin, Shu-Min, Lin, Horng-Chyuan, Wang, Chun-Hua, Yu, Chih-Teng, Kuo, Han-Pin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.01.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Aged; Antigens, CD - immunology; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - immunology; Antigens, Differentiation, Myelomonocytic - metabolism; Antineoplastic agents; Arginase - genetics; Arginase - metabolism; Biological and medical sciences; Blood Cell Count; Blotting, Western; Cancer Research; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; CD11b Antigen - immunology; CD11b Antigen - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cells, Cultured; Coculture Techniques; Female; Flow Cytometry; Hematology; Humans; Immune system; Internal Medicine; Jurkat Cells; Leukocytes, Mononuclear - cytology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lewis X Antigen - immunology; Lewis X Antigen - metabolism; Lipopolysaccharide Receptors - immunology; Lipopolysaccharide Receptors - metabolism; Lung cancer; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Myeloid Cells - immunology; Myeloid Cells - metabolism; Myeloid Cells - pathology; Neoplasm Staging; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Oncology; Original Paper; Pharmacology. Drug treatments; Pneumology; Sialic Acid Binding Ig-like Lectin 3; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Cytotoxic - pathology; Tumors of the respiratory system and mediastinum; T lymphocytes; Immunosuppression; Non-small-cell lung cancer (NSCLC); Myeloid-derived suppressor cells (MDSC); Human; Lung disease; Myeloid derived suppressor cell; Enzyme; Respiratory disease; Lung cancer; Alteration; Arginase; Patient; Malignant tumor; non-small cell lung carcinoma; Gene expression; Nitric-oxide synthase; T-Lymphocyte; Hydrolases; Bronchus disease; Advanced stage; Oxidoreductases; Cancer
• ISSN: 0171-5216; 1432-1335; 1432-1335
• DOI: 10.1007/s00432-009-0634-0

Background Immune aberrations have been demonstrated in tumorogenesis, and myeloid-derived suppressor cells (MDSC) have shown to play a pivotal role in mediating immune suppression in animal models of human tumors. In the present study, we explored the clinical relevance of CD11b⁺/CD14⁻/CD15⁺/CD33⁺ MDSCs and the association of MDSCs with CD8⁺ cytotoxic T lymphocytes in patients with non-small-cell lung cancer (NSCLC). Patients and methods The population of CD11b⁺/CD14⁻ cells in peripheral blood mononuclear cells (PBMNC) was determined in 173 patients with NSCLC and 42 control subjects. The expression of CD15, CD33, IL-4R, INF-γR, iNOS and l-arginase were analyzed. Cocultures with CD8⁺ T lymphocytes and Jurkat cells were developed to determine the impact of MDSCs on the expression of CD3ζ of CD8⁺ T lymphocytes. Results Patients with treatment-naïve, advanced-stage NSCLC (n = 87) had an increased subpopulation of CD11b⁺/CD14⁻/CD15⁺/CD33⁺ cells in the PBMNCs with characteristics of MDSCs (P < 0.0001). The CD11b⁺/CD14⁻ cells in PBMNC also express IL-4R and INF-γR and can suppress CD3ζ expression in CD8⁺ T lymphocytes. The subpopulation of CD11b⁺/CD14⁻ cells in PBMNC was decreased in the advanced-stage NSCLC patients who had responsiveness to chemotherapy (n = 41, P < 0.0001) and in the early-stage NSCLC patients after removal of tumor (n = 8, P = 0.0391). Notably, a negative association existed between the population of CD11b⁺/CD14⁻ cells in PBMNC and the frequency of CD8⁺ T lymphocytes (n = 48, r = −0.3141, P = 0.0297). Conclusions Our study provided evidence of an increased pool of CD11b⁺/CD14⁻/CD15⁺/CD33⁺ MDSCs in the peripheral blood of NSCLC patients. For the suppressive effect of the cells on CD8⁺ T lymphocytes, these findings suggest the important role of the CD11b⁺/CD14⁻/CD15⁺/CD33⁺ MDSCs in mediating immunosuppression in NSCLC.