Regulation of Antitumor Immune Responses by the IL-12 Family Cytokines, IL-12, IL-23, and IL-27

Figure 1

Molecular characterization of the IL-12 family cytokines, IL-12, IL-23, IL-27, and IL-35. IL-12 induces IFN-𝛾 production by NK and T cells and differentiation to Th1 cells. IL-23 induces IL-17 production by memory T cells and expands and maintains inflammatory Th17 cells. IL-27 induces the early Th1 differentiation and generation of IL-10-producing Tr1 cells. In addition, these cytokines induce distinct immune responses to tumors. IL-12 activates STAT4 and enhances antitumor cellular immunity through IFN-𝛾 production. IL-27 activates STAT1, as does IFN-𝛾 and STAT3 as well, and enhances antitumor immunity by augmenting cellular and humoral immunities. In contrast, although exogenously overexpressed IL-23 enhances antitumor immunity via memory T cells, endogenous IL-23 promotes protumor immunity through STAT3 activation by inducing inflammatory responses including IL-17 production.