Role of IFN-gamma produced after intraperitoneal transplantation of AK-5 cells in the induction of Fas ligand expression by tumor cells leading to immune evasion.

Abstract

AK-5 tumor cells expressed Fas-L on their surface after intraperitoneal transplantation in syngeneic animals. Fas-L expression by AK-5 cells is involved in the killing of the effector cells. Thus, the tumor has developed an escape mechanism from immune attack. In the present study, we showed that Fas-L expression on AK-5 cells is regulated by interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), as injection of antibodies against IFN-gamma downregulated the expression of Fas-L by tumor cells as determined by immunostaining and Northern hybridizations. Fas-L present on the tumor cells is biologically functional, as it induced DNA fragmentation in Fas+ YAC-1 cells. We have also shown shedding of Fas-L in cell-free ascitic fluid from tumor-bearing animals. These observations suggest that such cytokines as IFN-gamma and TNF-alpha play an important role in regulating the expression of Fas-L by AK-5 cells.