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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
- Source :
- Journal of Cancer Research and Clinical Oncology. 136:35-45
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- 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).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.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 (P0.0001). 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, P0.0001) 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).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.
- Subjects :
- Male
Cancer Research
Lung Neoplasms
Blotting, Western
Sialic Acid Binding Ig-like Lectin 3
Population
Lipopolysaccharide Receptors
Antigens, Differentiation, Myelomonocytic
Lewis X Antigen
Nitric Oxide Synthase Type II
non-small cell lung cancer (NSCLC)
CD8-Positive T-Lymphocytes
Biology
Jurkat Cells
Immune system
Antigen
Antigens, CD
Carcinoma, Non-Small-Cell Lung
medicine
Humans
Cytotoxic T cell
Myeloid Cells
education
Cells, Cultured
Aged
Neoplasm Staging
education.field_of_study
CD11b Antigen
Arginase
Cancer
General Medicine
Middle Aged
Flow Cytometry
medicine.disease
Coculture Techniques
Blood Cell Count
Oncology
Immunology
Leukocytes, Mononuclear
Myeloid-derived Suppressor Cell
Female
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 14321335 and 01715216
- Volume :
- 136
- Database :
- OpenAIRE
- Journal :
- Journal of Cancer Research and Clinical Oncology
- Accession number :
- edsair.doi.dedup.....0e604150bf30a14634ca8535e959c11f