Department of Medicine, Division of Oncology, Huntsman Cancer Institute / University of Utah, Salt Lake City, UT 84112, USA.
Department of Medical Oncology, Institut de Cancérologie de Strasbourg & Department of Functional Genomics & Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UNISTRA, Illkirch Cedex, Strasbourg, France.
Future Oncol. 2021 Apr;17(11):1401-1439. doi: 10.2217/fon-2020-0967. Epub 2021 Jan 21.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various cancers by reversing the immunosuppressive mechanisms employed by tumors to restore anticancer immunity. Although ICIs have demonstrated substantial clinical efficacy, patient response can vary in depth and duration, and many do not respond at all or eventually develop resistance. ICI resistance mechanisms can be tumor-intrinsic, related to the tumor microenvironment or patient-specific factors. Multiple resistance mechanisms may be present within one tumor subtype, or heterogeneity exists among patients with the same tumor type. Consequently, designing effective combination treatment strategies is challenging. This review will discuss ICI resistance mechanisms, and summarize findings from key preclinical and clinical trials of ICIs, to identify potential treatment strategies or pathways to overcome ICI resistance.
免疫检查点抑制剂 (ICIs) 通过逆转肿瘤用于恢复抗癌免疫的免疫抑制机制，彻底改变了各种癌症的治疗方法。尽管 ICI 已显示出显著的临床疗效，但患者的反应在深度和持续时间上可能存在差异，而且许多患者根本没有反应，或者最终产生耐药性。ICI 耐药机制可能是肿瘤内在的，与肿瘤微环境或患者特异性因素有关。同一肿瘤亚型内可能存在多种耐药机制，或者同一肿瘤类型的患者之间存在异质性。因此，设计有效的联合治疗策略具有挑战性。本综述将讨论 ICI 耐药机制，并总结 ICI 的关键临床前和临床试验结果，以确定克服 ICI 耐药性的潜在治疗策略或途径。
