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

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). 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-gamma R, 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 CD3 zeta of CD8(+) T lymphocytes. Patients with treatment-na < ve, 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-gamma R and can suppress CD3 zeta 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). 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.