文章：

干扰素的抗肿瘤作用：对癌症治疗的启示

Antitumour actions of interferons: implications for cancer therapy

原文发布日期：2016-02-25

DOI: 10.1038/nrc.2016.14

类型: Review Article

开放获取: 否

要点：

1. A thorough review of the literature on interferon (IFN) use in cancer, using breast cancer as a case study, with discussion of the few clinical studies with sufficient numbers and sufficiently robust design to draw any conclusions. The clinical successes of IFNs (in other cancers) are often in blood-borne cancers and/or the setting of low tumour burden.
2. New understanding of the immune response to tumours and its regulation by the different types of IFN provides exciting opportunities for redesigning when and how IFNs can be used in the clinic.
3. IFNs are produced by various cell types in the tumour microenvironment, where they can have direct effects on tumour cells or indirect effects via modulation of the immune response.
4. Technology-driven improvements in measuring IFN responses via transcriptomics (and potentially proteomics) provides insights into the signal transduction pathways activated or inactivated during tumorigenesis. They also provide 'signatures' that can indicate the potential responsivity of patients to particular forms of therapy, including IFN.
5. A telling example is the discovery that tumour-cell-derived, IRF7-driven, type I IFN activates the immune system to target the process of metastasis. This paves the way for the use of IFN therapy in an adjuvant setting.
6. There are indications requiring further study that IFN may work well in combination with other immune-based therapies (for example, checkpoint inhibitors that target the programmed cell death protein PD1 or its ligand, PDL1) or hormonal therapies for which synergistic effects might be expected because components of partner pathways are themselves IFN regulated.

要点翻译：

1. 以乳腺癌为例，对干扰素（IFN）在癌症治疗中应用的文献进行全面综述，重点讨论那些样本量充足、研究设计稳健且能得出明确结论的少数临床研究。干扰素在临床上的成功案例（见于其他癌症类型）多集中于血液系统肿瘤和/或低肿瘤负荷的情况。
2. 对肿瘤免疫应答及各型干扰素调控机制的新认识，为重新设计干扰素临床应用时机与方案提供了令人振奋的机遇。
3. 干扰素由肿瘤微环境中多种细胞产生，既可直接影响肿瘤细胞，也能通过调节免疫应答发挥间接作用。
4. 基于转录组学（及潜在蛋白质组学）的技术进步提升了干扰素应答检测能力，为揭示肿瘤发生过程中信号转导通路的激活/失活状态提供见解。这些技术还能提供表征患者对特定疗法（包括干扰素）潜在反应性的“特征谱”。
5. 一个典型例证是：研究发现肿瘤细胞来源、IRF7驱动的I型干扰素能激活免疫系统靶向转移过程。这为干扰素在辅助治疗中的应用铺平了道路。
6. 有迹象表明干扰素可能与其他免疫疗法（例如靶向程序性细胞死亡蛋白PD1及其配体PDL1的检查点抑制剂）或激素疗法产生协同效应——因为协同通路中的组分本身受干扰素调控，这些发现尚需进一步研究验证。

英文摘要：

The interferons (IFNs) are a family of cytokines that protect against disease by direct effects on target cells and by activating immune responses. The production and actions of IFNs are finely tuned to achieve maximal protection and avoid the potential toxicity associated with excessive responses. IFNs are back in the spotlight owing to mounting evidence that is reshaping how we can exploit this pathway therapeutically. As IFNs can be produced by, and act on, both tumour cells and immune cells, understanding this reciprocal interaction will enable the development of improved single-agent or combination therapies that exploit IFN pathways and new 'omics'-based biomarkers to indicate responsive patients.

摘要翻译： 

干扰素（IFNs）是一类细胞因子家族，通过直接作用于靶细胞以及激活免疫反应来抵御疾病。IFNs的产生和作用受到精细调控，以实现最大程度的保护，并避免过度反应可能带来的毒性。随着越来越多的证据重塑了我们如何利用这一通路进行治疗，IFNs再次成为研究热点。由于IFNs既可由肿瘤细胞也可由免疫细胞产生，并作用于这两类细胞，理解这种相互作用将有助于开发更有效的单药或联合疗法，利用IFNs通路以及新的“组学”生物标志物来识别有反应的患者。

原文链接：

Antitumour actions of interferons: implications for cancer therapy