Cell Death Research & Therapy (CDRT) Unit, Department for Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Cell Death Research & Therapy (CDRT) Unit, Department for Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium; Center for Cancer Biology (CCB), VIB, Leuven, Belgium.
Int Rev Cell Mol Biol. 2019;348:217-262. doi: 10.1016/bs.ircmb.2019.06.001. Epub 2019 Jun 20.
Type I interferons (IFNs) facilitate cancer immunosurveillance, antitumor immunity and antitumor efficacy of conventional cell death-inducing therapies (chemotherapy/radiotherapy) as well as immunotherapy. Moreover, it is clear that dendritic cells (DCs) play a significant role in aiding type I IFN-driven immunity. Owing to these antitumor properties several immunotherapies involving, or inducing, type I IFNs have received considerable clinical attention, e.g., recombinant IFNα2 or agonists targeting pattern recognition receptor (PRR) pathways like Toll-like receptors (TLRs), cGAS-STING or RIG-I/MDA5/MAVS. A series of preclinical and clinical evidence concurs that the success of anticancer therapy hinges on responsiveness of both cancer cells and DCs to type I IFNs. In this article, we discuss this link between type I IFNs and DCs in the context of cancer biology, with particular attention to mechanisms behind type I IFN production, their impact on DC driven anticancer immunity, and the implications of this for cancer immunotherapy, including DC-based vaccines.
I 型干扰素 (IFN) 促进癌症免疫监视、抗肿瘤免疫和常规诱导细胞死亡疗法（化疗/放疗）以及免疫疗法的抗肿瘤疗效。此外，树突状细胞 (DC) 在辅助 I 型 IFN 驱动的免疫中发挥着重要作用。由于这些抗肿瘤特性，涉及或诱导 I 型 IFNs 的几种免疫疗法受到了相当多的临床关注，例如重组 IFNα2 或针对模式识别受体 (PRR) 途径（如 Toll 样受体 (TLR)、cGAS-STING 或 RIG-I/MDA5/MAVS）的激动剂。一系列临床前和临床证据表明，癌症治疗的成功取决于癌细胞和 DC 对 I 型 IFNs 的反应性。在本文中，我们将讨论 I 型 IFN 和 DC 之间在癌症生物学中的联系，特别关注 I 型 IFN 产生的机制、它们对 DC 驱动的抗肿瘤免疫的影响，以及这对癌症免疫疗法的意义，包括基于 DC 的疫苗。
