CD95-Dependent T-Cell Killing by Glioma Cells Expressing CD95 Ligand: More on Tumor Immune Escape, the CD95 Counterattack, and the Immune Privilege of the Brain
Apparent failure of tumor-infiltrating lymphocytes to induce significant tumor cell death has been documented in numerous malignancies including malignant gliomas. T-cell suppression in glioma patients has commonly been attributed to soluble immunosuppressive factors such as transforming growth factor-β (TGF-β). However, more recently CD95 ligand expressed on tumor cells has also been shown to induce T-cell apoptosis. Here, we report that human malignant glioma cells express CD95 ligand and kill human Jurkat T cells via CD95/ CD95 ligand interactions. T-cell apoptosis is blocked when interactions of CD95 ligand expressed on glioma cells with CD95 expressed on T cells are inhibited competitively by soluble CD95 protein. Although glioma cells coexpress CD95 ligand and CD95 and are highly sensitive to CD95 antibody or soluble CD95 ligand, they neither commit suicide nor fratricide. We conclude that (i) susceptibility to CD95-mediated apoptosis involves crucial regulatory mechanisms other than levels of CD95 and CD95 ligand expression, and (ii) multiple mechanisms including soluble factors such as TGF-β and cell-derived signals such as CD95 ligand-induced signalling mediate immune escape of malignant brain tumors.