GBM Derived Gangliosides Induce T Cell Apoptosis through Activation of the Caspase Cascade Involving Both the Extrinsic and the Intrinsic Pathway.

Previously we demonstrated that human glioblastoma cell lines induce apoptosis in peripheral blood T cells through partial involvement of secreted gangliosides. Here we show that GBM-derived gangliosides induce apoptosis through involvement of the TNF receptor and activation of the caspase cascade. Culturing T lymphocytes with GBM cell line derived gangliosides (10-20 μg/ml) demonstrated increased ROS production as early as 18 hrs as indicated by increased uptake of the dye H2DCFDA while western blotting demonstrated mitochondrial damage as evident by cleavage of Bid to t-Bid and by the release of cytochrome-c into the cytosol.

Myeloid derived suppressor cell infiltration of murine and human gliomas is associated with reduction of tumor infiltrating lymphocytes.

Myeloid derived suppressor cells (MDSCs) are bone marrow derived cells with immunosuppressive properties. We have shown previously that MDSCs numbers are elevated in the circulation of GBM patients and that they produce reversible T cell dysfunction. Here, we evaluated whether MDSCs infiltrate human GBM tissues, and whether a commonly used mouse model of GBM reproduces the biology of MDSCs that is observed in patients.

Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma.

To assess the accumulation of myeloid-derived suppressor cells (MDSCs) in the peripheral blood of patients with glioma and to define their heterogeneity and their immunosuppressive function. Peripheral blood mononuclear cells (PBMCs) from healthy control subjects and from patients with newly diagnosed glioma were stimulated with anti-CD3/anti-CD28 and T cells assessed for intracellular expression of interferon (IFN)-γ. Antibody staining of PBMCs from glioma patients and healthy donors (CD33, HLADR, CD15, and CD14) followed by 4-color flow cytometry analysis-defined MDSC levels in the peripheral blood.

p300- and Myc-mediated regulation of glioblastoma multiforme cell differentiation.

Tumorigenic potential of glioblastoma multiforme (GBM) cells is, in part, attributable to their undifferentiated (neural stem cell-like) phenotype. Astrocytic differentiation of GBM cells is associated with transcriptional induction of Glial Fibrillary Acidic Protein (GFAP) and repression of Nestin, whereas the reciprocal transcription program operates in undifferentiated GBM cells. The molecular mechanisms underlying the regulation of these transcription programs remain elusive.