Potential clinical application of interleukin-27 as an antitumor agent.
Potential clinical application of interleukin-27 as an antitumor agent.
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DOI：
10.1111/cas.12731
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发表时间：
2015-09
期刊：
影响因子：
5.7
通讯作者：
Mizoguchi I
中科院分区：
文献类型：
--
作者：
Yoshimoto T;Chiba Y;Furusawa J;Xu M;Tsunoda R;Higuchi K;Mizoguchi I
癌症免疫疗法，如sipuleucel-T和ipilimumab，是利用免疫系统的力量对抗癌症并实现长期缓解的有希望的新疗法。白细胞介素(IL)-27是IL-12异二聚体细胞因子家族的一员，在调节免疫反应中具有多效性，具有促炎和抗炎特性。通过多种临床前小鼠模型获得的证据表明，IL-27通过多种机制对多种类型的肿瘤具有强大的抗肿瘤活性，且无明显的不良反应。这些机制不仅包括CD8+ T细胞、自然杀伤细胞和巨噬细胞介导的机制，还包括抗体依赖的细胞介导的细胞毒性、抗血管生成、直接抗增殖作用、抑制环氧化酶-2和前列腺素E2的表达以及抑制上皮-间质转化，这取决于个体肿瘤的特点。然而，IL-27亚基及其受体之一WSX-1在肿瘤细胞系移植后或内源性肿瘤发生易感性中的内源性作用似乎更为复杂。IL-27是一把双刃剑：IL-27增加IL-10的产生和程序性死亡配体1、T细胞免疫球蛋白和粘蛋白结构域3的表达，促进调节性T细胞的产生，IL-27受体α单点增强转化；IL-27也可能增强肿瘤效应。本文就IL-27的抗肿瘤作用和抗肿瘤作用两方面进行综述，并对IL-27作为抗肿瘤药物的临床应用前景进行探讨。
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.