Antitumor activity exhibited by Fas ligand (CD95L) overexpressed on lymphoid cells against Fas+ tumor cells

Abstract

Lymph node (LN) cells of Fas-mutant mice lpr/lpr (lpr) and lpr cg /lpr cg (lpr cg ) express an increased level of Fas ligand (FasL) (CD95L). We examined the antitumor potential of cell-bound FasL on these LN cells against Fas+ tumor cells. Fas+ F6b and Fas− N1d cells were produced from murine hepatoma MH134 (Fas−) by gene transfection. lpr and lpr cg LN cells inhibited growth of F6b but not N1d cells in vitro. Neither gld/gld lpr/lpr (gld/lpr) LN cells, which lack both FasL and Fas, nor wild-type LN cells showed growth-inhibitory activities against F6b and N1d cells. The effector cells and molecule were CD4−CD8− T cells and FasL, respectively. The tumor neutralization test and adoptive transfer demonstrated that lpr and lpr cg , but not gld/lpr, LN cells retarded the growth of F6b cells. Although anti-Fas antibody and FasL cause severe liver failure, wild-type mice injected with lpr LN cells appeared clinically normal. Adoptive transfer of lpr LN cells to F6b-bearing mice exerted the same antitumor activity in wild-type and gld/lpr recipient mice, indicating the applicability of cell-bound FasL for Fas-mediated target therapy of cancer. These results suggest that antitumor activity was dependent on the Fas-FasL system and that lymphoid cells overexpressing FasL can be powerful antitumor effector cells against Fas+ tumor cells.

DOI: 10.1007/s002620050514

6 Figures and Tables

Statistics

0100200'00'02'04'06'08'10'12'14'16
Citations per Year

85 Citations

Semantic Scholar estimates that this publication has 85 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Shimizu1998AntitumorAE, title={Antitumor activity exhibited by Fas ligand (CD95L) overexpressed on lymphoid cells against Fas+ tumor cells}, author={Motomu Shimizu and Yasutaka Takeda and Hideo Yagita and Takayuki Yoshimoto and Akio Matsuzawa}, journal={Cancer Immunology, Immunotherapy}, year={1998}, volume={47}, pages={143-148} }