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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

  • 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
Original Paper

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.

Keywords

Myeloid-derived suppressor cells (MDSC) T lymphocytes Non-small-cell lung cancer (NSCLC) Immunosuppression 

Notes

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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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Chien-Ying Liu
    • 1
  • Yu-Min Wang
    • 1
  • Chih-Liang Wang
    • 1
  • Po-Hao Feng
    • 1
  • How-Wen Ko
    • 1
  • Yun-Hen Liu
    • 2
  • Yi-Cheng Wu
    • 2
  • Yen Chu
    • 2
  • Fu-Tsai Chung
    • 1
  • Chih-Hsi Kuo
    • 1
  • Kang-Yun Lee
    • 1
  • Shu-Min Lin
    • 1
  • Horng-Chyuan Lin
    • 1
  • Chun-Hua Wang
    • 1
  • Chih-Teng Yu
    • 1
  • Han-Pin Kuo
    • 1
  1. 1.Department of Thoracic Medicine, Chang Gung Memorial Hospital, and School of MedicineChang Gung UniversityTaipeiTaiwan
  2. 2.Department of Thoracic Surgery, Chang Gung Memorial Hospital, and School of MedicineChang Gung UniversityTaipeiTaiwan

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