Figure 4.
Type I interferon and IL-12 mediate anti-TIM-3-mediated antitumor responses. (a–c) Tumor growth in CD11c-DTR mice given no treatment with diphtheria toxin (a) or treated with diphtheria toxin (b), and in NOD-SCID mice (c), left untreated (control) or inoculated subcutaneously with B16-F10 cells (1 × 105 cells per mouse) along with intratumoral injection of control plasmid DNA in the presence of isotype-matched control immunoglobulin or mAb to TIM-3, alone or with neutralizing anti-IFN-IR and anti-IL-12p40. (d) RT-PCR quantification of IFN-β1 and IL-12 mRNA in conventional DCs (cDC), plasmacytoid DCs (pDC), macrophages (MΦ), myeloid-derived suppressor cells (MDSC), natural killer cells (NK; left) or stromal cells isolated from B16 tumors grown in NOD-SCID mice (right), left untreated or treated with control plasmid DNA plus isotype-matched control immunoglobulin or mAb to TIM-3; results are presented relative to Actb expression. (e) Cytotoxicity of the cells in d (effector cells; E) cultured together for 6 h with B16 cells (target cells; T) at various ratios (E/T), assessed by lactate dehydrogenase–release assay. *P < 0.05 (paired Student's t-test). Data are representative of three experiments (a,c–e) or four experiments (b; error bars, s.e.m.).