title: T cell dependent and independent antitumor immunity generated by the expression of Fas ligand on mouse lung carcinoma cells.
abstract: Interaction between Fas and Fas ligand (FasL) induces apoptotic cell death of Fas-positive cells. Expression of FasL on tumors therefore possibly kills activated Fas-positive cytotoxic T cells that infiltrated into the tumors and consequently the tumors can evade from systemic immune responses. Previous studies however showed that forced expression of FasL in tumors induced neutrophil-mediated inflammatory reactions and accordingly produced T cell independent antitumor effects in the inoculated animals. We then analyzed the FasL-mediated antitumor responses with genetically mutated mice. Murine lung carcinoma (A11) cells transfected with the FasL gene (A11/FasL), which was able to kill Fas-positive B cells, did not form subcutaneous tumors and produced few lung spontaneous metastatic foci in immunocompetent mice. The mice that rejected A11/FasL cells developed tumor-specific protective immunity. A11/FasL cells were also rejected in T cell-defective nude mice and in CD18-deficient mice which showed impaired neutrophil functions, but not in Fas-defective (lpr/lpr) mutant mice. Antitumor activities on A11 cells were dependent on the number of co-injected A11/FasL cells but those on irrelevant B16 murine melanoma cells were not produced even with a large number of co-injected A11/FasL cells. In contrast to previous reports, the present study implies that T cells can also be effectors of FasL-mediated antitumor responses and neutrophils are not absolutely required for the responses.
authors.affiliation: Division of Pathology, Chiba Cancer Center Research Institute, Chuo-ku, Chiba 260-8717, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tada
authors.forename: Jiyang
authors.initials: J
authors.lastname: O-Wang
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuriyama
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tagawa
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014162:Transfection
chemical_list: D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins