Fas ligand-expressing tumors induce tumor-specific protective immunity in the inoculated hosts but vaccination with the apoptotic tumors suppresses antitumor immunity.
The interaction between Fas and Fas ligand (FasL) is involved in the apoptotic death of a number of cells including lymphocytes. Forced expression of FasL in tumors can induce apoptosis of infiltrating Fas-positive T cells; accordingly, tumors can survive in the milieu of systemic immune responses. However, FasL-expressing murine lung carcinoma (A11) and melanoma (B16) cells did not develop subcutaneous tumors and FasL-expressing A11 (A11/FasL) cells produced few spontaneous lung metastatic foci in syngeneic mice. The mice that rejected A11/FasL cells were resistant to subsequent challenge of parent A11 but not irrelevant B16 cells. Vaccination of mice with UV-treated A11/FasL, but not UV-treated A11 cells, however, augmented the growth rate of A11 but not B16 tumors, both of which were subsequently inoculated. The number of lung metastatic foci of A11 cells was also increased in the mice that received UV-treated A11/FasL but not UV-treated A11 cells. Intraperitoneal injection of UV-treated A11/FasL cells resulted in the production of larger amounts of immunosuppressive TGF-beta in peritoneal exudate than that of UV-treated A11 cells. Expression of the CD80 costimulatory molecule in tissues where UV-treated A11/FasL cells were inoculated was lower than the expression at an untreated A11/FasL-injected site. Our results indicated that apoptotic FasL-expressing tumor cells could impair host immune responses against the tumors, in contrast to potent antitumor immunity generated by viable FasL-expressing tumors.
Tada
Yuji
Y
Division of Pathology, Chiba Cancer Center Research Institute and Department of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
O-Wang
Jiyang
J
Wada
Akihiko
A
Takiguchi
Yuichi
Y
Tatsumi
Koichiro
K
Kuriyama
Takayuki
T
Sakiyama
Shigeru
S
Tagawa
Masatoshi
M
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D053222:Fas Ligand Protein; D005260:Female; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014611:Vaccination
D018122:B7-1 Antigen; D019496:Cancer Vaccines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta