| Malignant glioma patients are immunosuppressed, yet gliomas are highly infiltrated by monocytes/macrophages. Myeloid derived suppressor cells have been identified in other cancers and correlate with immune suppression and tumor burden. We hypothesized that glioma exposure causes normal monocytes to assume a myeloid-derived suppressor cell-like phenotype and that myeloid-derived suppressor cells are increased in glioma patients. By culturing normal CD14 + human monocytes with glioma cell lines we show that glioma-conditioned monocytes lack increased CD14 expression, increased immunosuppressive IL-10, TGF-beta, and B7-H1 expression, decreased phagocytic ability, and increased ability to induce apoptosis in activated lymphocytes, some of which are features of myeloid-derived suppressor cells. Glioma patients have increased circulating myeloid-derived suppressor cells and myeloid-derived suppressor cell precursors are increased in glioma-infiltrating monocytes in situ and U251-conditioned monocytes in vitro. Normal human monocytes exposed to glioma cells in vitro assume an immunosuppressive phenotype similar to myeloid derived suppressor cells described in other cancers. |
