Fas(CD95) ligand expression by tumor cell variants can be unrelated to their capacity to induce tolerance or immune rejection

According to the results of in vitro experiments, Fas(CD95) ligand expressi on by cancer cells might induce apoptosis of activated T cells and contribu te to immune tolerance. However, Fas ligand expression had never been explo red in vivo in tumor cell models yielding either immune response or toleran ce. In the present study, we analyzed the expression and function of Fas li gand in 2 clones of tumor cells originating from the same rat colon carcino ma. REGb cells were immunogenic and yielded tumors that regressed in immune -competent syngeneic hosts, whereas PROb cells induced active tolerance and yielded progressive tumors, pas ligand was expressed on the plasma membran e of both REGb and PROb cells, and its cDNA sequencing showed no mutation. However, neither REGb nor PROb cells induced apoptosis of co-cultured pas-s ensitive target cells. Our results show that surface expression of pas liga nd by tumor cells does not always induce killing of adjoining Fas-sensitive cells and that tumor cells may induce a protective immune response or an a ctive tolerance independently of Fas ligand expression. Int. J. Cancer 82:3 59-367, 1999. (C) 1999 Wiley-Liss, Inc.