C6 glioma cells retrovirally engineered to express IL-18 and Fas exert FasL-dependent cytotoxicity against glioma formation.
The decreased antitumor immune response significantly contributes to the progression of glioma. To evaluate whether the antitumor immunity is restored by stable co-expression of IL-18 and Fas receptor, we retrovirally introduced these two genes into rat C6 glioma cells. We found that IL-18-transduced glioma cells secreted IL-18 and induced PBMC IFN-gamma production in vitro. We also found that Fas-transduced glioma cells were susceptible to Fas-mediated apoptosis. In vivo, we found that IL-18 expression and Fas expression synergistically inhibited C6 cell tumorigenesis with the glioma cells being subcutaneously injected in rat flank. Furthermore, we found that co-expression of IL-18 and Fas also produced a marked survival advantage with the rats being intracerebrally implanted with the glioma cells. Finally, we demonstrated that FasL-dependent PBMC cytotoxicity participated in the anti-glioma immunity induced by IL-18 and Fas expression. Taken together, these findings demonstrate that increasing IL-18 production in tumor microenvironment and prompting functional Fas receptor expression of tumor cells could enhance FasL-dependent cytotoxic antitumor immunity.
Zhang
Yunhong
Y
Beijing Neurosurgical Institute, Capital University of Medical Science, Beijing 100050, China. zhangm@nsurg.wustl.edu
Wang
Chongcheng
C
Zhang
Yazhuo
Y
Sun
Meizhei
M
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D053222:Fas Ligand Protein; D018014:Gene Transfer Techniques; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019014:fas Receptor