Glioblastoma stem cells mediate immune suppression that can be inhibited with Jak2/Stat3 blockade

2012 Background: We have recently isolated as distinct subsets from glioblastoma tumors mesenchymal stem cells (gMSC) that are adherent, pleuripotent, CD73+, CD90+ and CD105+-expressing but non-tumorgenic and cancer stem cells (gCSC) that grow as neurospheres, CD133+-expressing and are tumorgenic in vivo. Mesenchymal stem cells have been shown to be immunosuppressive; however, the immune function and phenotype of gMSC and gCSC are unknown and the purpose of this study. Methods and Results: ELISA assays were used to determine the elaboration of immunosuppressive cytokines such as TGF- β (impairs antigen presentation and maintains Treg suppressor function), IL-6 (inhibits B cells, NKT, and T cells), IL-10 (inhibits Th1 function), VEGF (prevents dendritic cell maturation), and the Treg chemokine CCL-2 by gMSC and gCSC. Only gMSC (n=7) secrete CCL-2, TGF-β, VEGF, and IL-6, whereas gCSC (n=4) do not. In order to characterize the immunological phenotype of gMSC and gCSC, immune marker surface expression was eva...