Key role of IL-12 and IFN-γ in the antimetastatic effect of α-GalCer.
Groups of B6 WT, B6 gld, B6 pfp−/−, B6 TNF−/−, B6 IL-12−/−, B6 IL-18−/−, and B6 IFN-γ−/− mice or B6 WT mice treated with antimouse IFN-γ, antimouse TRAIL, antimouse IL-4, or control IgG1 mAb on days −1, 0 (the day of tumor inoculation), 4, 7, and 10 were inoculated (A) intravenously with 5 × 105 B16F10 tumor cells, (B) intrasplenically with 5 × 105 3LL tumor cells, or (C) intravenously with 1 × 105 of RM-1 tumor cells. Groups of BALB/c WT, BALB/c pfp−/−, BALB/c.CD1d−/−, BALB/c IFN-γ−/− mice or BALB/c WT mice treated with rabbit anti-asGM1 antibody on days −1, 0 (the day of tumor inoculation), and 7 were inoculated (D) intravenously with 1 × 106 DA3 tumor cells. Some groups of mice were treated intraperitoneally with 2 μg α-GalCer (▨) or vehicle control (▪) on days 0, 4, and 8 after tumor inoculation, as indicated. In all experiments, 14 days after tumor inoculation the lungs (B16F10, RM-1, DA3) or livers (3LL) of these mice were harvested, and tumor colonies were counted and recorded as the mean number of colonies ± SE. The number of mice in each group is indicated in parentheses, and asterisks indicate the groups in which α-GalCer treatment significantly reduced that group's number of lung or liver metastases (Mann-Whitney U: *P < .05; **P < .001).
