title: Tumor vaccination with macrophage colony-stimulating factor-producing Lewis lung carcinoma in mice.
abstract: Expression of various cytokines by cytokine gene-transduced tumor cells has been shown to increase antitumor immunity of tumor-bearing hosts. In the present study, macrophage-colony stimulating factor (M-CSF) cDNA was retrovirally transfected into Lewis lung carcinoma cells (3LL) of C57BL/6 mouse origin, and the effects of M-CSF expression were studied by inoculating syngeneic C57BL/6 mice with M-CSF-expressing 3LL cells. The mice inoculated with the lowest M-CSF-producing 3LL clone showed significant prolongation of the survival compared with wild-type 3LL-Inoculated mice, and 70% or more of the mice inoculated with 3LL clones with higher M-CSF production rejected inoculation. Mice injected with radiation-inactivated M-CSF-expressing 3LL cells before or after Inoculation of wild-type 3LL cells showed prolonged survival compared with mice injected with radiated control 3LL cells before or after transplantation of wild-type cells. In vivo depletion of effector subpopulations by injection of antibodies against CD4+ T cells, CD8+ T cells, or natural killer (NK) cells suggested involvement of NK cells and CD4+ T cells in M-CSF-mediated antitumor cytotoxicity in M-CSF-producing 3LL cells-inoculated mice. Severe combined immunodeficiency (SCID) mice with defective T- and B-cell function showed prolonged survival duration after inoculation with M-CSF-expressing 3LL cells compared with those transplanted with control 3LL cells, and this effect of M-CSF expression by 3LL-cells in SCID mice was also abolished by in vivo depletion of NK cells by antibody injection. These findings together with the previous reports that M-CSF augments antibody-dependent and-independent antitumor cytotoxicity suggest that M-CSF induces tumor immunity in this cytokine-expressing tumor-transplantation model.
authors.affiliation: Health Science Center, Kagawa University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Douzono
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: F
authors.initials: F
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Kawakami
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Motoyoshi
authors.forename: J
authors.initials: J
authors.lastname: Takahara
authors.forename: S
authors.initials: S
authors.lastname: Irino
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002277:Carcinoma / Q000473:pathology*; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D015316:Genetic Therapy; D006084:Graft Rejection; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000637:transplantation; D014611:Vaccination
chemical_list: D018076:DNA, Complementary; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor