CD95L mediates tumor counterattack in vitro but induces neutrophil-independent tumor rejection in vivo.
Many tumors express CD95L (CD178, FasL, APO-1L) and may thus kill tumor-infiltrating lymphocytes, a phenomenon called tumor counterattack. However, presently it is not clear whether tumor counterattack is a relevant immune escape mechanism. To characterize the effect of CD95L expression of tumor cells on tumor-specific T cells, we established an in vitro system with TCR tg T cells and a model tumor antigen. Preactivated antitumor T cells were able to kill CD95L(-) and CD95L(+) tumor cells. CD95L(+) tumor cells killed activated T cells in vitro and inhibited the expansion of cytotoxic antitumor T cells in mixed lymphocyte tumor reactions. In vivo CD95L expression led to delayed tumor growth or complete tumor rejection. Neutrophils were not responsible for the delayed growth of the CD95L(+) tumors tested. In mice with neutrophils deficient for important cytotoxicity mechanisms (p47phox(-/-) or iNOS(-/-) mice), CD95L(+) tumors grew similarly as in wild-type mice. Incidence and growth rate of CD95L(+) tumors in mice injected with a neutrophil-depleting or an isotype control antibody was the same. In CD95-deficient lpr mice, tumor growth was not altered as compared to wild-type mice. Taken together, CD95L mediated tumor counterattack in vitro, but led to neutrophil-independent tumor rejection in vivo.
Igney
Frederik H
FH
Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
Behrens
Christian K
CK
Krammer
Peter H
PH
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D019255:NADPH Oxidases; D009374:Neoplasms, Experimental / Q000276:immunology*; D009504:Neutrophils / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000172:deficiency; D052247:Nitric Oxide Synthase Type II; D010750:Phosphoproteins / Q000172:deficiency; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D019014:fas Receptor; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1