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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

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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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Acknowledgments

The authors would like to thank Ms. Ya-Ling Chang and Ms. Chih-Chen Ho in the Department of Thoracic Medicine of the Chang-Gung Memorial Hospital for assisting with the flow cytometric study. This work was funded by the National Science Council of Taiwan (NSC 97-2314-B-182A-091-MY2) and the Chang-Gung Memorial Hospital (CMRPG-371651 and CMRPG-376373).

Conflict of interest statement

The authors indicated no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Thoracic Medicine, Chang Gung Memorial Hospital, and School of Medicine, Chang Gung University, No. 199, Tun-Hwa North Road, Taipei, 105, Taiwan

    Chien-Ying Liu, Yu-Min Wang, Chih-Liang Wang, Po-Hao Feng, How-Wen Ko, Fu-Tsai Chung, Chih-Hsi Kuo, Kang-Yun Lee, Shu-Min Lin, Horng-Chyuan Lin, Chun-Hua Wang, Chih-Teng Yu & Han-Pin Kuo

  2. Department of Thoracic Surgery, Chang Gung Memorial Hospital, and School of Medicine, Chang Gung University, Taipei, Taiwan

    Yun-Hen Liu, Yi-Cheng Wu & Yen Chu

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Correspondence to Chien-Ying Liu or Chih-Teng Yu.

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C.-Y. Liu, Y.-M. Wang, and C.-L. Wang contributed equally to the work on this project as first authors.

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Liu, CY., Wang, YM., Wang, CL. et al. 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. J Cancer Res Clin Oncol 136, 35–45 (2010). https://doi.org/10.1007/s00432-009-0634-0

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