Nature Medicine
2, 1361 - 1366 (1996)
doi:10.1038/nm1296-1361
Lymphocyte apoptosis induced by CD95 (APO−1/Fas) ligand−expressing tumor cells — A mechanism of immune evasion?Susanne Strand1, Walter J. Hofmann2, Hubert Hug3, Martina Müller1, Gerd Otto4, Dennis Strand5, Sara M. Mariani6, Wolfgang Stremmel1, Peter H. Krammer6
& Peter R. Galle1, 7
1Department of Gastroenterology, University Hospital, Bergheimerstrasse 58, 69115 Heidelberg, Germany
2Institute of Pathology, Im Neuenheimer Feld 220, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
3Center of Molecular Biology (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
4Department of Surgery, University Hospital, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
5Department of Developmental Genetics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
6Tumorimmunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
7Correspondence should be addressed to P.R.G. The CD95 (APO−1/Fas) system is an important mediator of T−cell cytotoxicity. We investigated this system in 22 hepatocellular carcinomas (HCCs) from patients. All HCCs had partially or completely lost the expression of the CD95 receptor constitutively expressed by normal liver cells and might thus evade CD95−mediated killing. We also considered a new mechanism of immune evasion, namely, the active destruction of T−lymphocytes by tumor cells expressing CD95 ligand (CD95L). CD95L messenger RNA and protein could be detected in the HCCs. In coculture experiments, HepG2 hepatoblastoma cells, expressing CD95L mRNA after treatment with cytostatic drugs, killed CD95+ Jurkat lymphocytes. Our data suggest that tumor cells can evade immune attack by down−regulation of the CD95 receptor and killing of lymphocytes through expression of CD95L.
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