The renal cell carcinoma lysis by a specific cytotoxic T cell clone is independent of the Fas/Fas-L cytotoxic pathway.
The expression of Fas antigen at the surface of renal cell carcinoma and the susceptibility to Fas-mediated lysis by a tumor specific CTL clone were investigated. Renal cell carcinoma cell lines expressed Fas antigen and were susceptible to apoptosis mediated by antibodies to Fas/APO1. Using RT-PCR, we further showed that these cell lines expressed mRNA for Fas deleted transmembrane region, corresponding to a soluble form of Fas/APO-1. To investigate the role of the Fas/FasL pathway in the cytotoxic response against RCC cells, we analyzed the induction of Fas-L on a tumor specific T cell clone (CTL8C2), previously generated against one RCC cell line. Fas-L expression on CTL8C2 was detected by RT-PCR after stimulation with autologous tumor cells. However, the cytotoxic activity of CTL8C2 was completely abolished when EGTA was added, suggesting that the cytolysis was mainly mediated by a Ca+2-dependent pathway, perforin/granzyme-based.
Caignard
A
A
INSERM Cytokines et Immunité Anti-tumorale, Institut Gustave Roussy, Villejuif, France.
Guillard
M
M
Cai
Z
Z
Asselin-Paturel
C
C
Carayol
G
G
Chouaib
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D002461:Cell Line, Transformed; D002999:Clone Cells; D053222:Fas Ligand Protein; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology*; D017384:Sequence Deletion; D015398:Signal Transduction / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor