Open AccessPotential clinical application of interleukin‐27 as an antitumor agent
Author(s) -
Yoshimoto Takayuki,
Chiba Yukino,
Furusawa JunIchi,
Xu Mingli,
Tsunoda Ren,
Higuchi Kaname,
Mizoguchi Izuru
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12731
Subject(s) - immune system , cancer research , biology , cytokine , immunology , cd8 , ipilimumab , tumor microenvironment , cytotoxic t cell , immunotherapy , biochemistry , in vitro
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 CD 8 + 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 2 , 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.