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Role of type I interferon in inducing a protective immune response: Perspectives for clinical applications

机译:I型干扰素在诱导保护性免疫应答中的作用:临床应用前景

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Type I IFNs (IFN-I) are antiviral cytokines endowed with many biological effects, including antitumor activity. Over the last 15 years, an ensemble of studies has revealed that these cytokines play a crucial role in the induction of a protective antitumor immune response. Early in vivo studies in mouse models have been instrumental for understanding the IFN-I-induced host-mediated mechanisms. IFN-alpha is currently recognized as a powerful inducer of the differentiation/activation of dendritic cells (DCs) and today IFN-alpha-conditioned DCs represent promising DC candidates for the development of therapeutic cancer vaccines. Moreover, data from pilot clinical trials support the concept of using IFN-alpha as an enhancer of the response of patients to cancer vaccines. Notably, endogenous IFN-I production does also play a critical role in the antitumor response to some chemotherapeutic agents. Thus, we can now envisage new strategies of clinical use of IFN-alpha, based on the injection of IFN-conditioned cells as well as the usage of these cytokines as cancer vaccine adjuvants, alone or in combination with other treatments (including epigenetic drugs) to induce an immunogenic cell death and a long lasting antitumor response. (C) 2014 Elsevier Ltd. All rights reserved.
机译:I型干扰素(IFN-I)是具有许多生物学作用,包括抗肿瘤活性的抗病毒细胞因子。在过去的15年中,大量研究表明这些细胞因子在诱导保护性抗肿瘤免疫反应中起着至关重要的作用。在小鼠模型中进行的早期体内研究有助于理解IFN-I诱导的宿主介导的机制。 IFN-α目前被认为是树突状细胞(DC)分化/激活的强大诱导剂,如今,以IFN-α为条件的DC代表了开发治疗性癌症疫苗的有希望的DC候选物。此外,来自中试临床试验的数据支持使用IFN-α作为患者对癌症疫苗反应增强剂的概念。值得注意的是,内源性IFN-1的产生在对某些化学治疗剂的抗肿瘤应答中也起着关键作用。因此,我们现在可以设想基于注射IFN条件的细胞以及将这些细胞因子单独或与其他治疗方法(包括表观遗传药物)组合使用的新策略,以临床应用IFN-α的方式以及这些细胞因子作为癌症疫苗佐剂的用途诱导免疫原性细胞死亡和持久的抗肿瘤反应。 (C)2014 Elsevier Ltd.保留所有权利。

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