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 significa nt tumor cell death has been documented in numerous malignancies inclu ding malignant gliomas, T-cell suppression in glioma patients has comm only been attributed to soluble immunosuppressive factors such as tran sforming growth factor-beta (TGF-beta). However, more recently CD95 li gand expressed on tumor cells has also been shown to induce T-cell apo ptosis, Here, we report that human malignant glioma cells express CD95 ligand and kill human Jurkat T cells via CD95/CD95 ligand interaction s, T-cell apoptosis is blocked when interactions of CD95 ligand expres sed on glioma cells with CD95 expressed on T cells are inhibited compe titively 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 t hat (i) susceptibility to CD95-mediated apoptosis involves crucial reg ulatory mechanisms other than levels of CD95 and CD95 ligand expressio n, and (ii) multiple mechanisms including soluble factors such as TGF- beta and cell-derived signals such as CD95 ligand-induced signalling m ediate immune escape of malignant brain tumors.