ABSTRACT

Introduction: Innate immunity is armed with interferons (IFNs) that link innate immunity to adaptive immunity to generate long-term and protective immune responses against invading pathogens and tumors. However, regulation of IFN production is crucial because chronic IFN responses can have deleterious effects on both antitumor and antimicrobial immunity in addition to provoking autoinflammatory or autoimmune conditions.

Areas covered: Here, we focus on the accumulated evidence on antimicrobial and antitumor activities of type I and II IFNs. We first summarize the intracellular and intercellular mechanisms regulating IFN production and signaling. Then, we discuss the mechanisms modulating the dual nature of IFNs for both antitumor and antimicrobial immune responses. Finally, we review the detrimental role of IFNs for induction of autoinflammation and autoimmunity.

Expert opinion: The current evidence suggests that the dual role of IFNs for antimicrobial and antitumor immunity is dependent not only on the timing, administration route, and dose of IFNs but also on the type of pathogen/tumor. Therefore, we think that combinatorial therapies involving IFN-inducing adjuvants and immune-checkpoint blockers may offer therapeutic potential, especially for cancer, whereas infectious, autoinflammatory or autoimmune diseases require fine adjustment of timing, dose, and route of the administration for candidate IFN-based vaccines or immunotherapies.

摘要

简介：先天免疫由干扰素 (IFN) 武装起来，干扰素将先天免疫与适应性免疫联系起来，以产生针对入侵病原体和肿瘤的长期保护性免疫反应。然而，调节干扰素的产生至关重要，因为除了引发自身炎症或自身免疫疾病外，慢性干扰素反应还可能对抗肿瘤和抗菌免疫产生有害影响。

涵盖的领域：在这里，我们专注于关于 I 型和 II 型 IFN 的抗菌和抗肿瘤活性的累积证据。我们首先总结了调节 IFN 产生和信号传导的细胞内和细胞间机制。然后，我们讨论了调节 IFN 对抗肿瘤和抗菌免疫反应的双重性质的机制。最后，我们回顾了干扰素对诱导自身炎症和自身免疫的有害作用。

专家意见：目前的证据表明，干扰素对抗菌和抗肿瘤免疫的双重作用不仅取决于干扰素的时间、给药途径和剂量，还取决于病原体/肿瘤的类型。因此，我们认为涉及 IFN 诱导佐剂和免疫检查点阻滞剂的组合疗法可能提供治疗潜力，特别是对于癌症，而感染性、自身炎症或自身免疫性疾病需要微调候选 IFN-的给药时间、剂量和途径。基于疫苗或免疫疗法。