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J Cancer Res Clin Oncol. 2010 Jan;136(1):35-45. doi: 10.1007/s00432-009-0634-0.

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.

Author information

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. cyliu01@adm.cgmh.org.tw

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.

PMID:
19572148
DOI:
10.1007/s00432-009-0634-0
[Indexed for MEDLINE]

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