Vaccination of apoptotic Fas ligand-expressing tumors decreased antitumor responses by enhanced production of immunosuppressive cytokines.
Expression of Fas ligand (FasL) in tumors produced antitumor effects by generating both inflammation and T cell-mediated immunity, although the Fas/FasL interaction induces an apoptotic process of Fas-positive activated T cells. Our previous study, however, showed that immunization of mice with ultraviolet (UV)-treated FasL-expressing tumors rather induced immune suppression to the tumors, whereas mice rejected UV-untreated FasL-expressing tumors and developed protective immunity subsequently. Since dendritic cells (DCs) control tumor-specific immune responses in vivo, we examined a possible role of DCs in the immune suppression induced. Administration of DCs that were co-cultured with UV-treated FasL-expressing tumors did not influence the growth of parent tumors that were subsequently inoculated. Migration of immunocompetent cells into UV-treated FasL-expressing tumors was not significantly different from that into UV-untreated FasL-expressing tumors. However, production of immunosuppressive but not T helper type 1 cytokines was enhanced when UV-treated FasL-expressing tumors were administered. These data collectively suggest that the immune suppression induced by UV-treated FasL-expressing tumors was not attributable to tolerance of DCs, but due to cytokine-induced suppression of cell-mediated immunity.
Wada
Akihiko
A
Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
Tada
Yuji
Y
Shimozato
Osamu
O
Takiguchi
Yuichi
Y
Tatsumi
Koichiro
K
Kuriyama
Takayuki
T
Tagawa
Masatoshi
M
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D053222:Fas Ligand Protein; D005260:Female; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive / Q000379:methods; D008175:Lung Neoplasms / Q000276:immunology* / Q000628:therapy; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014466:Ultraviolet Rays
D019496:Cancer Vaccines; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins