Expression of FasL by tumor cells does not abrogate anti-tumor CTL function.
The effects of Fas-ligand (FasL) expression by tumor cells on their tumorigenicity and immunogenicity have been reported as opposite, contradictory results. In some systems the killing of Fas positive cytotoxic T-cells (CTL) by FasL expressing tumors resulted in increased tumorigenicity while in other systems tumors expressing FasL were eliminated by neutrophil mediated inflammation. In the present study, we investigated how FasL expression influences the low immunogenic Lewis lung carcinoma clone D122 and its highly immunogenic MHC I (H-2Kb) and B7-1 (CD80) transfectant 39.5-B7, by transfecting the human FasL (FasL) gene into these cells. Despite the fact that FasL-expressing cells kill effectively appropriate target cells (L1210-fas) compared to parental cells (D122) and low expressors (DFasL-33), these tumor cells were completely rejected in syngeneic mice (C57BL/6), but not in Fas mutant B6-MRL mice, suggesting that functional Fas receptor expression in the host was required to induce an anti-tumor mechanism. In addition, although FasL-expressing immunogenic tumor cells (39.5-B7-FasL 7) kill effectively target cells in vitro, both the transfectant and the mock transfectant (39.5-B7-pBabe) were rejected in syngenic mice. The sensitivity of FasL expressing tumor cells to lysis by CTLs was similar to that of FasL non-expressors. Therefore, these results indicate that FasL expression on immunogenic tumor cells does not affect their immunogenicity in vivo, as well as CTL functions in vitro.
Lee
Sung-Hyung
SH
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. lilee@wisemail.weizmann.ac.il
Bar-Haim
Erez
E
Goldberger
Ofir
O
Reich-Zeliger
Shlomit
S
Vadai
Ezra
E
Tzehoval
Esther
E
Eisenbach
Lea
L
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009154:Mutation / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger