Dual Roles of IL-27 in Cancer Biology and Immunotherapy.
Dual Roles of IL-27 in Cancer Biology and Immunotherapy.
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DOI：
10.1155/2017/3958069
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发表时间：
2017
影响因子：
4.6
通讯作者：
Ferrini S
中科院分区：
文献类型：
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作者：
Fabbi M;Carbotti G;Ferrini S
IL-27是一种多效性双链细胞因子，由EBI3和IL-27p28亚基组成，在结构上与IL-12和IL-6细胞因子家族相关。 IL-27 通过由 IL-27Rα (WSX1) 和 gp130 链组成的异二聚体受体发挥作用，该受体主要通过 STAT1 和 STAT3 介导信号传导。 IL-27 最初被报道为一种免疫增强细胞因子，与 IL-12 协同作用，支持 CD4+ T 细胞增殖、辅助性 T (Th)1 细胞分化和 IFN-γ 产生。然而，随后的研究表明，IL-27 表现出复杂的免疫调节功能，这可能导致与所考虑的生物背景和实验模型相关的促炎或抗炎作用。在临床前肿瘤模型中获得的几项证据表明，IL-27 具有有效的抗肿瘤活性，不仅与诱导肿瘤特异性 Th1 和细胞毒性 T 淋巴细胞 (CTL) 反应有关，而且还与对肿瘤细胞增殖、存活、侵袭性和血管生成潜力的直接抑制作用有关。尽管如此，鉴于其免疫调节功能，IL-27 对癌症的影响可能是双重的，并且也可能发生促肿瘤效应。在这里，我们将总结 IL-27 的生物学活性及其与 IFN 的功能重叠，并根据其在癌症免疫治疗中的潜在应用讨论其在肿瘤中的双重作用。
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.