T cell dependent and independent antitumor immunity generated by the expression of Fas ligand on mouse lung carcinoma cells.
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.
Tada
Yuji
Y
Division of Pathology, Chiba Cancer Center Research Institute, Chuo-ku, Chiba 260-8717, Japan.
O-Wang
Jiyang
J
Takiguchi
Yuichi
Y
Tatsumi
Koichiro
K
Kuriyama
Takayuki
T
Tagawa
Masatoshi
M
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
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins