Increased Circulating Immunosuppressive CD14 + HLA-DR −/Low Cells Correlate with Clinical Cancer Stage and Pathological Grade in Patients with Bladder Carcinoma

Abstract

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.