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 expression by cancer cells might induce apoptosis of activated T cells and contribute to immune tolerance. However, Fas ligand expression had never been explored in vivo in tumor cell models yielding either immune response or tolerance. In the present study, we analyzed the expression and function of Fas ligand in 2 clones of tumor cells originating from the same rat colon carcinoma. REGb cells were immunogenic and yielded tumors that regressed in immunecompetent syngeneic hosts, whereas PROb cells induced active tolerance and yielded progressive tumors. Fas ligand was expressed on the plasma membrane of both REGb and PROb cells, and its cDNA sequencing showed no mutation. However, neither REGb nor PROb cells induced apoptosis of co-cultured Fas-sensitive target cells. Our results show that surface expression of Fas ligand 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 active tolerance independently of Fas ligand expression.
Department of Biology and Therapy of Cancer, INSERM U517, Faculty of Medicine, University of Burgundy, Dijon, France.
N
N
Favre
B
B
Bonnotte
N
N
Droin
A
A
Fromentin
E
E
Solary
F
F
Martin
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D017209:Apoptosis; D002999:Clone Cells; D003513:Cycloheximide / Q000494:pharmacology; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000032:analysis*
D000954:Antigens, Surface; D011500:Protein Synthesis Inhibitors; D019014:fas Receptor; D003513:Cycloheximide