Increased circulating immunosuppressive CD14(+)HLA-DR(-/low) cells correlate with clinical cancer stage and pathological grade in patients with bladder carcinoma

J Int Med Res. 2011;39(4):1381-91. doi: 10.1177/147323001103900424.


This study investigated CD14(+)HLA-DR(-/low) cells in peripheral blood mononuclear cells (PBMCs) from 64 patients with bladder carcinoma (BC) and 14 healthy controls. Cell phenotypes were determined and CD14(+)HLA-DR(-/low) cells, CD14(+)HLA-DR(+) cells and PBMCs depleted of CD14(+)HLA-DR(-/low) cells were isolated. Proliferation of stimulated PBMCs and interferon-γ (IFN-γ) production after addition of CD14(+)HLA-DR(-/low) and CD14(+)HLA-DR(+) cells at different ratios were measured. IFN-γ production was also measured after addition of L-arginine and/or antitransforming growth factor-β (TGF-β) neutralizing monoclonal antibody, and in PBMCs depleted of CD14(+)HLA-DR(-/low) cells. The proportion of CD14(+)HLA-DR(-/low) cells in BC patients was significantly higher than in controls. CD14(+)HLA-DR(-/low) cells significantly decreased T-cell proliferation and IFN-γ production in a dose-dependent manner. This suppressive activity was partially reversed by L-arginine or anti-TGF-β. Enhanced IFN-γ secretion was also seen in PBMCs depleted of CD14(+)HLA-DR(-/low) cells. The level of CD14(+)HLA-DR(-/low) cells was associated with gender, tumour size, number of tumours, cancer pathological grade and clinical stage. CD14(+)HLA-DR(-/low) cells may represent a subpopulation of myeloid-derived suppressor cells in BC patients.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arginase / metabolism
  • Arginine / metabolism
  • Case-Control Studies
  • Cell Proliferation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • HLA-DR Antigens / blood
  • HLA-DR Antigens / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology*
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharide Receptors / immunology*
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Myeloid Cells / immunology
  • Myeloid Cells / metabolism
  • Myeloid Cells / pathology
  • Neoplasm Staging
  • Phenotype
  • T-Lymphocytes / immunology
  • Transforming Growth Factor beta / metabolism
  • Urinary Bladder / immunology
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*


  • HLA-DR Antigens
  • Lipopolysaccharide Receptors
  • Transforming Growth Factor beta
  • Interferon-gamma
  • Arginine
  • Arginase