title: Potential clinical application of interleukin-27 as an antitumor agent.
abstract: 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 (IL)-27, a member of the IL-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 IL-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 CD8(+) 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 E2 , and suppression of epithelial-mesenchymal transition, depending on the characteristics of individual tumors. However, the endogenous role of IL-27 subunits and one of its receptor subunits, WSX-1, in the susceptibility to tumor development after transplantation of tumor cell lines or endogenously arising tumors seems to be more complicated. IL-27 functions as a double-edged sword: IL-27 increases IL-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 IL-27 receptor α singling enhances transformation; IL-27 may augment protumor effects as well. Here, we review both facets of IL-27, antitumor effects and protumor effects, and discuss the potential clinical application of IL-27 as an antitumor agent.
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshimoto
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Yukino
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Furusawa
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Mingli
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Tsunoda
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
authors.forename: Izuru
authors.initials: I
authors.lastname: Mizoguchi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D064094:Interleukin-27 / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D064094:Interleukin-27
keywords: IL-10; IL-27; Treg; antitumor effects; protumor effects