Control of apoptosis in Epstein Barr virus-positive nasopharyngeal carcinoma cells: Opposite effects of CD95 and CD40 stimulation

The expression and function of CD95 and CD40 were investigated in malignant cells from EBV-positive undifferentiated nasopharyngeal carcinomas (NPCs), Large amounts of CD95 and CD40 expression were detected in 15 of 16 EBV-po sitive NPC specimens. In contrast, CD95 was not detected in two biopsies fr om patients with EBV-negative differentiated NPCs, We tested whether the CD 95 apoptotic pathway was functional in NPC cells by treating two EBV-positi ve NPC tumor lines in vitro with a CD95 agonist, In both cases, NPC cells w ere extremely susceptible to CD95-mediated apoptosis, despite strong consti tutive expression of Bcl-x, Combined CD40 and CD95 stimulation was used to investigate the possible anti-apoptotic activity mediated by CD40. The CD40 receptor was activated by incubating NPC cells with murine L cells produci ng CD154, the CD40 ligand, This treatment resulted in a strong inhibition o f CD95-related cytotoxicity. Such an anti-apoptotic effect of CD40 is well known for B lymphocytes, but has not previously been reported for epithelia l cells. These data suggest that NPC tumor-infiltrating lymphocytes, which often produce the CD40 ligand ill situ, may increase the survival of malign ant cells, thereby enhancing tumor growth in patients.