I型干扰素（IFN）是一类拥有双重作用的促炎细胞因子，对恶性转化、肿瘤进展和治疗反应发挥作用。一方面，强有力的、急性的和能够消除的I型干扰素反应已被证明具有明显的抗癌作用，这不仅体现了其对（至少一些）恶性细胞的直接细胞周期停滞/细胞毒作用，还体现了它们显著的免疫刺激功能。与此观点一致的是，I型干扰素信号转导已被认为参与各种免疫原性治疗的抗肿瘤效果，包括（但不限于）诱导免疫原性细胞死亡（ICD）的药物和免疫检查点抑制剂（ICIs）。另一方面，弱、慢性和无法消除的I型干扰素反应已被证明支持肿瘤进展和对治疗的抗药性，这反映了亚优型I型干扰素信号转导在介导细胞保护性作用、促进干细胞特性、有利于对染色体不稳定性的耐受性以及有助于建立免疫耗竭的肿瘤微环境方面的能力。本文将对I型干扰素信号转导的基本方面进行综述，并讨论其在恶性转化、肿瘤进展和对治疗的反应中有所依赖的影响。© 2023作者。由John Wiley & Sons Ltd.出版的Immunological Reviews出版。

Type I interferon (IFN) is a class of proinflammatory cytokines with a dual role on malignant transformation, tumor progression, and response to therapy. On the one hand, robust, acute, and resolving type I IFN responses have been shown to mediate prominent anticancer effects, reflecting not only their direct cytostatic/cytotoxic activity on (at least some) malignant cells, but also their pronounced immunostimulatory functions. In line with this notion, type I IFN signaling has been implicated in the antineoplastic effects of various immunogenic therapeutics, including (but not limited to) immunogenic cell death (ICD)-inducing agents and immune checkpoint inhibitors (ICIs). On the other hand, weak, indolent, and non-resolving type I IFN responses have been demonstrated to support tumor progression and resistance to therapy, reflecting the ability of suboptimal type I IFN signaling to mediate cytoprotective activity, promote stemness, favor tolerance to chromosomal instability, and facilitate the establishment of an immunologically exhausted tumor microenvironment. Here, we review fundamental aspects of type I IFN signaling and their context-dependent impact on malignant transformation, tumor progression, and response to therapy.© 2023 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.