Expression of Fas ligand is not a main mechanism used by tumors to counteract antitumor immunity.
The role of Fas ligand (FasL) in tumor immune privilege is controversial. In this study, 22 human tumor cell lines reported to be FasL+ were reevaluated by Western blot analysis, ELISA, and a functional assay. None of the cells lines expressed FasL. To assess whether human tumors express FasL in vivo, susceptibility to FasL-mediated killing was evaluated. About 75% of the 22 tumors tested were sensitive to FasL-mediated apoptosis, suggesting, therefore, that only about 25% could possibly express FasL. To investigate whether "FasL+" human tumor cells could suppress the proinflammatory effects of FasL in vivo, FasL transfectants were generated from two prototype "FasL+" tumor cell lines. The transfectants expressing FasL were rejected by SCID mice. In contrast, all the mice inoculated with parental tumor cells developed large tumors. These results suggested that human tumor cells that express FasL and resist both FasL-mediated apoptosis and inflammation are rare or nonexistant. We concluded that FasL expression is not a main mechanism that tumors use to counteract antitumor immunity.
Chen
Chuan-min
CM
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Song
Wenying
W
Kao
John Y
JY
Zheng
Qiong-duan
QD
Chen
Jian-Jun
JJ
D000818:Animals; D000918:Antibody Specificity; D016923:Cell Death; D004306:Dose-Response Relationship, Immunologic; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007109:Immunity; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009369:Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor