Potential clinical application of interleukin‐27 as an antitumor agent

<jats:p>Cancer immunotherapies such as sipuleucel‐T and ipilimumab are promising new treatments that harness the power of the immune system to fight cancer and achieve long‐lasting remission. Interleukin (<jats:styled-content style="fixed-case">IL</jats:styled-content>)‐27, a member of the <jats:styled-content style="fixed-case">IL</jats:styled-content>‐12 heterodimeric cytokine family, has pleiotropic functions in the regulation of immune responses with both pro‐inflammatory and anti‐inflammatory properties. Evidence obtained using a variety of preclinical mouse models indicates that <jats:styled-content style="fixed-case">IL</jats:styled-content>‐27 possesses potent antitumor activity against various types of tumors through multiple mechanisms without apparent adverse effects. These mechanisms include those mediated not only by <jats:styled-content style="fixed-case">CD</jats:styled-content>8<jats:sup>+</jats:sup> T cells, natural killer cells and macrophages, but also by antibody‐dependent cell‐mediated cytotoxicity, antiangiogenesis, direct antiproliferative effects, inhibition of expression of cyclooxygenase‐2 and prostaglandin E<jats:sub>2</jats:sub>, and suppression of epithelial–mesenchymal transition, depending on the characteristics of individual tumors. However, the endogenous role of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐27 subunits and one of its receptor subunits, <jats:styled-content style="fixed-case">WSX</jats:styled-content>‐1, in the susceptibility to tumor development after transplantation of tumor cell lines or endogenously arising tumors seems to be more complicated. <jats:styled-content style="fixed-case">IL</jats:styled-content>‐27 functions as a double‐edged sword: <jats:styled-content style="fixed-case">IL</jats:styled-content>‐27 increases <jats:styled-content style="fixed-case">IL</jats:styled-content>‐10 production and the expression of programmed death ligand 1 and T‐cell immunoglobulin and mucin domain‐3, and promotes the generation of regulatory T cells, and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐27 receptor α singling enhances transformation; <jats:styled-content style="fixed-case">IL</jats:styled-content>‐27 may augment protumor effects as well. Here, we review both facets of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐27, antitumor effects and protumor effects, and discuss the potential clinical application of <jats:styled-content style="fixed-case">IL</jats:styled-content>‐27 as an antitumor agent.</jats:p>