Department of Medicine, Division of Medical Oncology, University of Colorado School of Medicine, Aurora, Colorado.
Immunol Rev. 2019 Jul;290(1):6-23. doi: 10.1111/imr.12766.
Immune checkpoint inhibitors (ICIs) have revolutionized our approach to cancer treatment in the past decade. While monoclonal antibodies to CTLA-4 and PD-1/PD-L1 have produced remarkable and durable responses in a subset of patients, the majority of patients will still develop primary or adaptive resistance. With complex mechanisms of resistance limiting the efficacy of checkpoint inhibitor monotherapy, it is critical to develop combination approaches to allow more patients to benefit from immunotherapy. In this review, I approach the current landscape of ICI research from the perspective of sarcomas, a rare group of bone and soft tissue cancers that have had limited benefit from checkpoint inhibitor monotherapy, and little investigation of biomarkers to predict responses. By surveying the various mechanisms of resistance and treatment modalities being explored in other solid tumors, I outline how ICIs will undoubtedly serve as the critical foundation for future directions in modern immunotherapy.
免疫检查点抑制剂 (ICIs) 在过去十年中彻底改变了我们的癌症治疗方法。虽然针对 CTLA-4 和 PD-1/PD-L1 的单克隆抗体在一部分患者中产生了显著且持久的反应，但大多数患者仍会出现原发性或适应性耐药。由于耐药的复杂机制限制了检查点抑制剂单药治疗的疗效，因此开发联合治疗方法至关重要，以使更多患者从免疫治疗中获益。在这篇综述中，我从肉瘤的角度探讨了当前的 ICI 研究现状，肉瘤是一组罕见的骨和软组织癌症，它们从检查点抑制剂单药治疗中获益有限，并且很少有针对预测反应的生物标志物的研究。通过调查其他实体瘤中正在探索的各种耐药机制和治疗方式，我概述了 ICI 无疑将成为现代免疫治疗未来方向的关键基础。
