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Mediators of Inflammation
Volume 2017 (2017), Article ID 3958069, 14 pages
https://doi.org/10.1155/2017/3958069
Review Article

Dual Roles of IL-27 in Cancer Biology and Immunotherapy

Laboratory of Biotherapy, IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genoa, Italy

Correspondence should be addressed to Silvano Ferrini

Received 31 October 2016; Revised 23 December 2016; Accepted 12 January 2017; Published 1 February 2017

Academic Editor: Dmitri V. Krysko

Copyright © 2017 Marina Fabbi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

IL-27 is a pleiotropic two-chain cytokine, composed of EBI3 and IL-27p28 subunits, which is structurally related to both IL-12 and IL-6 cytokine families. IL-27 acts through a heterodimer receptor consisting of IL-27Rα (WSX1) and gp130 chains, which mediate signaling predominantly through STAT1 and STAT3. IL-27 was initially reported as an immune-enhancing cytokine that supports CD4+ T cell proliferation, T helper (Th)1 cell differentiation, and IFN-γ production, acting in concert with IL-12. However, subsequent studies demonstrated that IL-27 displays complex immune-regulatory functions, which may result in either proinflammatory or anti-inflammatory effects in relationship to the biological context and experimental models considered. Several pieces of evidence, obtained in preclinical tumor models, indicated that IL-27 has a potent antitumor activity, related not only to the induction of tumor-specific Th1 and cytotoxic T lymphocyte (CTL) responses but also to direct inhibitory effects on tumor cell proliferation, survival, invasiveness, and angiogenic potential. Nonetheless, given its immune-regulatory functions, the effects of IL-27 on cancer may be dual and protumor effects may also occur. Here, we will summarize IL-27 biological activities and its functional overlaps with the IFNs and discuss its dual role in tumors in the light of potential applications to cancer immunotherapy.