Differences in the molecular mechanisms to induce antitumor effects between IL-12 and IL-27. IL-27 utilizes several mechanisms to induce antitumor effects depending on characteristics of individual tumors. Against highly immunogenic tumors expressing MHC class I, IL-27 exerts antitumor effects by mainly CD8⁺ T cells. However, against poorly immunogenic tumors lacking expression of IL-27R, IL-27 has to use other mechanisms including NK cells and antiangiogenesis to exert its antitumor effects. In contrast, IL-12 has a strong antitumor effect through high production of IFN- by NK and T cells. This high IFN- production also causes systemic toxicities, which leads to limitation of the IL-12 therapy in clinical trials.