Functional analysis of CD14⁺HLA-DR^-/low myeloid-derived suppressor cells in patients with lung squamous cell...

Immunomodulatory therapy is a potential effective treatment for advanced cancer that may provide an alternative to chemotherapy, which patients can experience adverse side effects to. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to cause T-cell tolerance in rodents and humans; however, little is known about the role of MDSCs in squamous cell carcinoma. In the present study, the role of MDSCs in lung squamous cell carcinoma was investigated. Peripheral blood from 78 patients with lung squamous cell carcinoma and 30 healthy controls was examined for the presence and function of human MDSCs, denoted as monocyte differentiation antigen CD14-positive HLA class II histocompatibility antigen DR-negative/low (CD14⁺ HLA-DR^-/low) cells by flow cytometry. The sorted T-cell surface glyoprotein CD3 (CD3)⁺ cells and CD14⁺HLA-DR^-/low cells were subsequently co-cultured with a tumor cell line (NCI-H226). T-cell apoptosis was detected using annexin-V-fluorescein isothicyanate and 7-aminoactinomycin D. Interferon-γ (IFN-γ) levels were detected using an ELISA. The frequency of MDSCs in the peripheral blood mononuclear cells (PBMCs) from patients with lung squamous cell carcinoma was significantly higher compared with that of the healthy controls (P<0.05), whereas the frequency of T-cell surface glyoprotein CD4 (CD4)⁺ T cells and CD8⁺ T cells in PBMCs was significantly decreased (P<0.05). In an MDSC/CD8⁺ co-culture system, the proportion of CD8⁺ T-cell apoptosis significantly increased with the increase in ratio of MDSCs (P<0.05), while the proportion of tumor cell apoptosis significantly decreased (P<0.05). The concentration of IFN-γ significantly decreased with the increase in MDSCs (P<0.05). Therefore, MDSCs participate in the immune escape of lung squamous cell carcinoma, and may provide a possible therapeutic strategy for the treatment of this disease.