Zhao Xianda, Wangmo Dechen, Robertson Matthew, Subramanian Subbaya
Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
Cancers (Basel). 2020 May 5;12(5):1161. doi: 10.3390/cancers12051161.
Immune checkpoint blockade therapy (ICBT) has revolutionized the treatment and management of numerous cancers, yet a substantial proportion of patients who initially respond to ICBT subsequently develop resistance. Comprehensive genomic analysis of samples from recent clinical trials and pre-clinical investigation in mouse models of cancer provide insight into how tumors evade ICBT after an initial response to treatment. Here, we summarize our current knowledge on the development of acquired ICBT resistance, by examining the mechanisms related to tumor-intrinsic properties, T-cell function, and tumor-immune cell interactions. We discuss current and future management of ICBT resistance, and consider crucial questions remaining in this field of acquired resistance to immune checkpoint blockade therapies.
免疫检查点阻断疗法（ICBT）彻底改变了多种癌症的治疗和管理方式，然而，很大一部分最初对ICBT有反应的患者随后会产生耐药性。对近期临床试验样本的全面基因组分析以及在癌症小鼠模型中的临床前研究，有助于深入了解肿瘤在对治疗产生初始反应后如何逃避ICBT。在此，我们通过研究与肿瘤内在特性、T细胞功能以及肿瘤-免疫细胞相互作用相关的机制，总结了我们目前对获得性ICBT耐药性发展的认识。我们讨论了ICBT耐药性的当前和未来管理方法，并思考了在这一获得性免疫检查点阻断疗法耐药领域中仍然存在的关键问题。
