HonorHealth Research Institute, Scottsdale, AZ, USA.
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Drugs. 2020 Apr;80(5):459-465. doi: 10.1007/s40265-020-01270-7.
Immune checkpoint inhibitors (ICIs), monoclonal antibodies to cytotoxic T-lymphocyte-associated protein 4, programmed cell death 1 or its ligand PD-L1 are rapidly changing the treatment landscape and prognosis of many cancer types. Following their initial approval in melanoma in 2011, ICIs are now approved in many other cancers. Despite the long-term, durable response that can be noted with ICIs, the majority of patients do not respond to ICIs and some of the initial responders develop relapsed disease during their treatment course. In order to improve the response rate to ICIs, an understanding of the mechanisms of resistance is critical. Given the number of different ways cancers can become resistant to ICIs, patient-rather than population-based strategies to reverse resistance will likely be needed. We review the currently defined mechanisms of resistance to ICIs and discuss possible methods to overcome these mechanisms.
免疫检查点抑制剂（ICIs）是针对细胞毒性 T 淋巴细胞相关蛋白 4、程序性细胞死亡 1 或其配体 PD-L1 的单克隆抗体，正在迅速改变许多癌症类型的治疗前景和预后。继 2011 年在黑色素瘤中首次获得批准后，ICIs 现在已在许多其他癌症中获得批准。尽管 ICI 可以观察到长期、持久的反应，但大多数患者对 ICI 没有反应，一些初始反应者在治疗过程中出现疾病复发。为了提高对 ICI 的反应率，了解耐药机制至关重要。鉴于癌症对抗 ICI 产生耐药性的方式有很多种，可能需要针对患者而不是针对人群的策略来逆转耐药性。我们回顾了目前定义的对 ICI 的耐药机制，并讨论了克服这些机制的可能方法。
