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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.