Urothelial carcinoma (UC) is the most common form of bladder cancer (BC) and is the variant with the most immunogenic response. This makes urothelial carcinoma an ideal candidate for immunotherapy with immune checkpoint inhibitors. Key immune checkpoint proteins PD-1 and CTLA-4 are frequently expressed on T-cells in urothelial carcinoma. The blockade of this immune checkpoint can lead to the reactivation of lymphocytes and augment the anti-tumor immune response. The only immune checkpoint inhibitors that are FDA-approved for metastatic urothelial carcinoma target the programmed death-1 receptor and its ligand (PD-1/PD-L1) axis. However, the overall response rate and progression-free survival rates of these agents are limited in this patient population. Therefore, there is a need to find further immune-bolstering treatment combinations that may positively impact survival for patients with advanced UC. In this review, the current immune checkpoint inhibition treatment landscape is explored with an emphasis on combination therapy in the form of PD-1/PD-L1 with CTLA-4 blockade. The investigation of the current literature on immune checkpoint inhibition found that preclinical data show a decrease in tumor volumes and size when PD-1/PD-L1 is blocked, and similar results were observed with CTLA-4 blockade. However, there are limited investigations evaluating the combination of CTLA-4 and PD-1/PD-L1 blockade. We anticipate this review to provide a foundation for a deeper experimental investigation into combination immune checkpoint inhibition therapy in metastatic urothelial carcinoma.
尿路上皮癌是膀胱癌最常见的类型，也是免疫原性反应最强的亚型。这一特性使其成为免疫检查点抑制剂治疗的理想对象。在尿路上皮癌中，T细胞表面常表达PD-1与CTLA-4等关键免疫检查点蛋白。阻断这些免疫检查点可重新激活淋巴细胞功能，增强抗肿瘤免疫应答。目前美国食品药品监督管理局批准用于转移性尿路上皮癌的免疫检查点抑制剂仅针对程序性死亡受体-1及其配体通路。然而该患者群体对现有药物的总体应答率与无进展生存率仍存在局限，因此亟需探索能改善晚期尿路上皮癌患者生存获益的新型免疫联合治疗方案。本综述系统梳理了当前免疫检查点抑制治疗格局，重点探讨PD-1/PD-L1抑制剂与CTLA-4抑制剂联合治疗策略。现有文献研究表明：临床前数据显示阻断PD-1/PD-L1通路可显著缩小肿瘤体积，CTLA-4阻断也观察到类似效果，但关于双通路联合阻断的研究仍较为有限。本综述旨在为深入开展转移性尿路上皮癌联合免疫检查点抑制治疗的实验研究提供理论基础。
肿瘤(癌症)患者之家