Princess Margaret Cancer Centre, University Health Network Toronto, Ontario M5G 2M9, Canada; email:
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Annu Rev Pathol. 2021 Jan 24;16:167-198. doi: 10.1146/annurev-pathol-031920-093932. Epub 2020 Dec 2.
The immune system is tasked with identifying malignant cells to eliminate or prevent cancer spread. This involves a complex orchestration of many immune cell types that together recognize different aspects of tumor transformation and growth. In response, tumors have developed mechanisms to circumvent immune attack. Type I interferons (IFN-Is) are a class of proinflammatory cytokines produced in response to viruses and other environmental stressors. IFN-Is are also emerging as essential drivers of antitumor immunity, potently stimulating the ability of immune cells to eliminate tumor cells. However, a more complicated role for IFN-Is has arisen, as prolonged stimulation can promote feedback inhibitory mechanisms that contribute to immune exhaustion and other deleterious effects that directly or indirectly permit cancer cells to escape immune clearance. We review the fundamental and opposing functions of IFN-Is that modulate tumor growth and impact immune function and ultimately how these functions can be harnessed for the design of new cancer therapies.
免疫系统的任务是识别恶性细胞，以消除或防止癌症扩散。这涉及到许多免疫细胞类型的复杂协调，这些细胞共同识别肿瘤转化和生长的不同方面。作为回应，肿瘤已经发展出逃避免疫攻击的机制。I 型干扰素 (IFN-Is) 是一类在病毒和其他环境应激源的刺激下产生的促炎细胞因子。IFN-Is 也被认为是抗肿瘤免疫的重要驱动因素，强烈刺激免疫细胞消除肿瘤细胞的能力。然而，IFN-Is 发挥了更复杂的作用，因为长期刺激会促进反馈抑制机制，导致免疫衰竭和其他有害影响，这些影响直接或间接地使癌细胞逃避免疫清除。我们回顾了调节肿瘤生长和影响免疫功能的 IFN-Is 的基本和相反功能，以及这些功能如何被用于设计新的癌症治疗方法。
