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

Abstract EN

The 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-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 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)-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.