Bedke J, Stühler V, Todenhöfer T, Stenzl A
Klinik für Urologie, Eberhard Karls Universität Tübingen, Hoppe-Seyler-Str. 3, 72070, Tübingen, Deutschland.
Urologe A. 2018 Nov;57(11):1301-1308. doi: 10.1007/s00120-018-0787-z.
Immune checkpoint inhibitors (ICI) have significantly improved the systemic therapy of metastatic disease in genitourinary malignancies. With the European Medicines Agency (EMA) approval of the antibodies nivolumab and pembrolizumab directed against programmed cell death 1 (PD-1) as well as the PD-L1 antibody atezolizumab, three agents are available for the treatment of metastatic urothelial carcinoma and renal cell carcinoma. This article describes the underlying mode of action of PD-1/PD-L1 blockade and other ICIs to activate the immune system for effective tumor rejection. Future therapeutic strategies are focusing on the combination of ICI with targeted therapies to enhance the immune defense, especially in the local tumor microenvironment. A further clinical need exists for the establishment of biomarkers to predict a therapy response under ICI, in particular for the role of the PD-L1 status. Biomarkers for predicting primary or acquired therapy resistance are also of clinical importance to enable good patient selection for ICI therapy.
免疫检查点抑制剂（ICI）显著改善了泌尿生殖系统恶性肿瘤转移性疾病的全身治疗。随着欧洲药品管理局（EMA）批准针对程序性细胞死亡蛋白1（PD-1）的抗体纳武单抗和派姆单抗以及PD-L1抗体阿特珠单抗，有三种药物可用于治疗转移性尿路上皮癌和肾细胞癌。本文描述了PD-1/PD-L1阻断及其他ICI激活免疫系统以有效排斥肿瘤的潜在作用机制。未来的治疗策略集中于将ICI与靶向治疗联合以增强免疫防御，尤其是在局部肿瘤微环境中。建立生物标志物以预测ICI治疗反应，特别是PD-L1状态的作用，存在进一步的临床需求。预测原发性或获得性治疗耐药的生物标志物对ICI治疗的良好患者选择也具有临床重要性。
