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lüll Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27 Xu M; Mizoguchi I; Morishima N; Chiba Y; Mizuguchi J; Yoshimoto TClin Dev Immunol 2010[]; 2010 (ä): äThe interleukin (IL)-12 family, which is composed of heterodimeric cytokines including IL-12, IL-23, and IL-27, is produced by antigen-presenting cells such as macrophages and dendritic cells and plays critical roles in the regulation of helper T (Th) cell differentiation. IL-12 induces IFN-gamma 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 regulatory T cells. In addition, these cytokines induce distinct immune responses to tumors. IL-12 activates signal transducers and activator of transcription (STAT)4 and enhances antitumor cellular immunity through interferon (IFN)-gamma production. IL-27 activates STAT1, as does IFN-gamma 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.|Antigen-Presenting Cells/*metabolism[MESH]|Cell Differentiation[MESH]|Gene Expression Regulation/immunology[MESH]|Humans[MESH]|Interleukin-12/*immunology/metabolism[MESH]|Interleukin-17/immunology/metabolism[MESH]|Interleukin-23/immunology/metabolism[MESH]|Neoplasms/*immunology[MESH]|T-Lymphocytes, Helper-Inducer/cytology/immunology[MESH] |