Hargadon Laboratory, Department of Biology, Hampden-Sydney College, Hampden-Sydney, VA, 23943, USA.
Br J Dermatol. 2021 Dec;185(6):1095-1104. doi: 10.1111/bjd.20608. Epub 2021 Sep 7.
Immune checkpoint blockade (ICB) therapy has achieved unprecedented success in the treatment of metastatic melanoma, though its efficacy is often limited by innate and acquired mechanisms of resistance. Type I and type II interferons (IFNs) act as key determinants of checkpoint blockade therapeutic outcome, and tumour-intrinsic and -extrinsic factors that disrupt IFN activity confer resistance to various checkpoint inhibitors. This review highlights our current understanding of the mechanisms by which tumours disrupt IFN function in the context of ICB, and it discusses therapeutic strategies to overcome these mechanisms of resistance and improve the clinical reach of ICB therapy in patients with melanoma.
免疫检查点阻断 (ICB) 治疗在转移性黑色素瘤的治疗中取得了前所未有的成功，但其疗效常常受到先天和获得性耐药机制的限制。I 型和 II 型干扰素 (IFNs) 是检查点阻断治疗效果的关键决定因素，而破坏 IFN 活性的肿瘤内在和外在因素赋予了对各种检查点抑制剂的耐药性。这篇综述强调了我们目前对肿瘤在 ICB 背景下破坏 IFN 功能的机制的理解，并讨论了克服这些耐药机制和提高 ICB 治疗黑色素瘤患者临床疗效的治疗策略。
