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Journal of Cancer Research and Clinical Oncology

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01.01.2010 | Original Paper

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

verfasst von: Chien-Ying Liu, Yu-Min Wang, Chih-Liang Wang, Po-Hao Feng, How-Wen Ko, Yun-Hen Liu, Yi-Cheng Wu, Yen Chu, Fu-Tsai Chung, Chih-Hsi Kuo, Kang-Yun Lee, Shu-Min Lin, Horng-Chyuan Lin, Chun-Hua Wang, Chih-Teng Yu, Han-Pin Kuo

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2010

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Abstract

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.

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Titel: 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
verfasst von: Chien-Ying Liu
Yu-Min Wang
Chih-Liang Wang
Po-Hao Feng
How-Wen Ko
Yun-Hen Liu
Yi-Cheng Wu
Yen Chu
Fu-Tsai Chung
Chih-Hsi Kuo
Kang-Yun Lee
Shu-Min Lin
Horng-Chyuan Lin
Chun-Hua Wang
Chih-Teng Yu
Han-Pin Kuo
Publikationsdatum: 01.01.2010
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-009-0634-0

Springer Medizin

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