Type I Interferons and Cancer: An Evolving Story Demanding Novel Clinical Applications
Type I Interferons and Cancer: An Evolving Story Demanding Novel Clinical Applications
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DOI：
10.3390/cancers11121943
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发表时间：
2019-12-01
期刊：
影响因子：
5.2
通讯作者：
Belardelli, Filippo
中科院分区：
文献类型：
--
作者：
Arico, Eleonora;Castiello, Luciano;Belardelli, Filippo
关于干扰素α/β（IFN-I）在小鼠中的抗肿瘤作用的第一份报告发表于50年前。IFN-α是FDA批准用于癌症临床的第一种免疫抑制药物。然而，它们的临床使用发生在它们的大多数作用机制仍然未知的时候。这些细胞因子被用作常规的细胞生长抑制药物或非特异性生物反应调节剂。随后归因于IFN-I的特定生物学活性在其临床应用中被考虑得很差。值得注意的是，在人类和小鼠中的大量数据强调了由免疫细胞和肿瘤细胞产生的内源性IFN-I在控制肿瘤生长和对抗肿瘤治疗的反应中的重要性。虽然许多肿瘤学家认为IFN-I是“死药”，但最近的研究揭示了新的作用机制，其在癌症控制和免疫治疗反应或抗性中具有潜在意义，这为它们在靶向和个性化抗癌治疗中的使用提供了新的理论基础。在这篇展望文章中，我们关注以下几个方面：（1）IFN-I在增强标准抗癌治疗的抗肿瘤作用方面的附加价值（2）IFN-1在肿瘤干细胞生长调控中的作用及其对开发新型抗肿瘤治疗的可能意义;和（3）IFN-1在癌症疫苗开发中的作用和通过离体IFN-刺激的树突细胞的原位递送提供的有趣的治疗可能性。
The first report on the antitumor effects of interferon alpha/beta (IFN-I) in mice was published 50 years ago. IFN-alpha were the first immunotherapeutic drugs approved by the FDA for clinical use in cancer. However, their clinical use occurred at a time when most of their mechanisms of action were still unknown. These cytokines were being used as either conventional cytostatic drugs or non-specific biological response modifiers. Specific biological activities subsequently ascribed to IFN-I were poorly considered for their clinical use. Notably, a lot of the data in humans and mice underlines the importance of endogenous IFN-I, produced by both immune and tumor cells, in the control of tumor growth and in the response to antitumor therapies. While many oncologists consider IFN-I as "dead drugs", recent studies reveal new mechanisms of action with potential implications in cancer control and immunotherapy response or resistance, suggesting novel rationales for their usage in target and personalized anti-cancer treatments. In this Perspectives Article, we focus on the following aspects: (1) the added value of IFN-I for enhancing the antitumor impact of standard anticancer treatments (chemotherapy and radiotherapy) and new therapeutic approaches, such as check point inhibitors and epigenetic drugs; (2) the role of IFN-I in the control of cancer stem cells growth and its possible implications for the development of novel antitumor therapies; and (3) the role of IFN-I in the development of cancer vaccines and the intriguing therapeutic possibilities offered by in situ delivery of ex vivo IFN-stimulated dendritic cells.