Induction of T cell apoptosis by glioblastoma multiforme

Glioblastoma multiforme is the most common and malignant brain tumor in adults. Despite an intensive treatment regimen the average survival after diagnosis remains only 15 months. Novel therapies are desperately needed. While recent successes with immune based therapies, in targeting brain tumors, are promising widespread clinical efficacy has yet to be demonstrated. Glioblastoma patients are systemically immune suppressed and to increase the effectiveness of immune based therapies these immunosuppressive pathways must be neutralized. A possible role for glioblastoma-derived exosomes in immune suppression has never been investigated. Exosomes are small membrane-bound vesicles of endocytic origins that contain mRNA and proteins and are secreted by a variety of cell types, including brain tumors. We have shown that glioblastoma-derived exosomes are capable of decreasing T cell viability. In order to delineate the signaling pathway responsible for reduced T cell viability a Fas neutralizing antibody was utilized which yielded enigmatic results. However, glioblastoma-derived exosomes activated a caspase cascade indicative of Fas signaling and the activation of the extrinsic apoptotic pathway. This is a novel form of immune suppression in glioblastoma and could lead to the development of novel therapies.