Systemic IL-12–dependent IFN-γ production after vaccination is required for lymphoma growth inhibition. WT or genetic cytokine knockout mice were challenged with 1 × 10⁵ Eμ-myc 299 tumor cells and treated on day 5 with irradiated, α-GalCer–loaded tumor cells, or left untreated. (A) Eμ-myc tumor burden in blood 19 days after tumor inoculation, in untreated or vaccine-treated WT, IFN-γ^KO, IL-12^KO (p35^KO and p40^KO), and IL-18^KO mice. As indicated, some WT mice received mAb-based depletion of IFN-γ or isotype control mAb (cIg). (B) Serum cytokine levels from Eμ-myc tumor-bearing WT mice 24 hours after vaccination compared with untreated mice. (C) IFN-γ levels in serum from WT, NKT cell–deficient (Jα18^KO), and IL-12–deficient (IL-12p35^KO) mice at various time points relative to vaccination. Data are mean ± SEM; n = 5 mice. ND indicates not detected. ***P < .0001 (unpaired t test). ns indicates not significant. Two or 3 independent experiments were performed.