LYMPHOCYTE APOPTOSIS INDUCED BY CD95 (APO-1 FAS) LIGAND-EXPRESSING TUMOR-CELLS - A MECHANISM OF IMMUNE EVASION/

The CD95 (APO-1/Fas) system is an important mediator of T-cell cytotox icity. We investigated this system in 22 hepatocellular carcinomas (HC Cs) from patients. All HCCs had partially or completely lost the expre ssion of the CD95 receptor constitutively expressed by normal liver ce lls and might thus evade CD95-mediated killing. We also considered a n ew mechanism of immune evasion, namely, the active destruction of T-ly mphocytes by tumor cells expressing CD95 ligand (CD95L). CD95L messeng er RNA and protein could be detected in the HCCs. In coculture experim ents, HepG2 hepatoblastoma cells, expressing CD95L mRNA after treatmen t with cytostatic drugs, killed CD95(+) jurkat lymphocytes. Our data s uggest that tumor cells can evade immune attack by downregulation of t he CD95 receptor and killing of lymphocytes through expression of CD95 L.