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Background: The importance of ectoenzymes CD39 and CD73 in mediating adenosinergic immunosuppression has been recognized, but their roles in human malignant glioma-associated immunosuppression remain largely unknown., Methods: In this study, the ectoenzyme characteristics of malignant glioma cells and infiltrating CD4(+) T lymphocytes isolated from newly diagnosed malignant glioma patients were investigated. The ectoenzyme activities of both cell populations were determined by nucleotide hydrolysis assay. The immunosuppressive property of the CD39-CD73 synergic effect was evaluated via responder T-cell proliferation assay., Results: We observed that CD39(-)CD73(+) glioma cells and infiltrating CD4(+)CD39(high)CD73(low) T lymphocytes exhibited 2 distinct but complementary ectoenzyme phenotypes, which were further verified by enzyme activity assay. The nucleotide hydrolysis cascade was incomplete unless CD39 derived from T lymphocytes and CD73 collaborated synergistically. We demonstrated that increased suppression of responder CD4(+) T-cell proliferation suppression was induced by CD4(+)CD39(+) T cells in the presence of CD73(+) glioma cells, which could be alleviated by the CD39 inhibitor ARL67156, the CD73 inhibitor APCP, or the adenosine receptor A2aR antagonist SCH58261. In addition, survival analysis suggested that CD73 downregulation was a positive prognostic factor related to the extended disease-free survival of glioblastoma patients., Conclusions: Our data indicate that glioma-derived CD73 contributes to local adenosine-mediated immunosuppression in synergy with CD39 from infiltrating CD4(+)CD39(+) T lymphocytes, which could become a potential therapeutic target for treatment of malignant glioma and other immunosuppressive diseases.

Human peripheral blood monocytes are a heterogeneous population, including CD14(+) CD16(-) 'classical' monocytes and CD14(+) CD16(+) 'proinflammatory' monocytes. CD16(+) monocytes are expanded in various inflammatory conditions. However, little is known about the CD14(+) CD16(+) monocytes in patients with breast cancer. We detected CD14(+) CD16(+) monocytes in 96 patients with breast cancer and 54 control subjects using flow cytometry. Receiver-operating characteristic (ROC) curve analysis was used to determine the feasibility of CD14(+) CD16(+) monocytes as an indicator for diagnosis of breast cancer. We found that the frequency of CD14(+) CD16(+) monocytes showed a significantly greater increase in breast cancer patients than in controls (16·96% versus 10·84%, P < 0·0001). The area under the ROC curve for CD14(+) CD16(+) monocytes was 0·805 [95% confidence interval (95% CI): 0·714-0·877, P = 0·0001]. Furthermore, the levels of CD16(+) monocytes were significantly negatively associated with the tumour size and pathological staging. In vitro, we showed that CD14(+) CD16(+) monocytes were expanded significantly when the purified CD14(+) monocytes were exposed to Michigan Cancer Foundation (MCF)-7 cells-conditioned medium (MCF-CM) or, separately, to monocyte chemotactic protein 1 (MCP-1). Neutralizing antibodies against MCP-1 inhibited the expansion of CD14(+) CD16(+) monocytes by MCF-CM. Collectively, our findings indicated that MCP-1 can expand CD14(+) CD16(+) monocytes in patients with breast cancer. Furthermore, the CD14(+) CD16(+) monocyte may be a useful indicator in early diagnosis of breast cancer., (© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.)