Fas-mediated apoptosis in tumor formation and defense.

Survival of cells that usually die by apoptosis contributes to tumor formation. Fas ligand is a specific death factor that induces apoptosis by binding to its receptor Fas. Expression of Fas ligand in tumor cells resistant to Fas-mediated apoptosis helps the tumor to escape surveillance by the immune system. It induces killing of Fas expressing tissue cells as well as killing of lymphocytes that attack and remove tumor cells. Inducing apoptosis in the attacking lymphocytes resembles the mechanism of how Fas ligand contributes to the maintenance of immune privilege. Some cytostatic drugs used in chemotherapy kill their target cells by upregulating expression of Fas and inducing Fas ligand expression in the same cell by different mechanisms. The cells then undergo suicide or fratricide. Tumor cells which became resistant to Fas-mediated apoptosis should be insensitive to cytotoxic drugs that kill drug-sensitive cells by inducing the Fas system. Therefore, depending on the cell type, the Fas system plays complex roles in the origin, survival and killing of tumors.