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

Research output: Contribution to journalArticle

201 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)35-45
Number of pages11
JournalJournal of Cancer Research and Clinical Oncology
Volume136
Issue number1
DOIs
Publication statusPublished - Jan 2010
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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