Recent FDA approvals of regimens targeting programmed death 1 (PD-1) in combination with anti-CTLA-4 or with VEGF tyrosine kinase inhibitors are reshaping front-line therapy for metastatic kidney cancer. In parallel, therapeutics specific for programmed death ligand 1 (PD-L1), one of the two major ligands for PD-1, are under continued investigation. Surprisingly, not all PD-1 and PD-L1 agents lead to similar clinical outcomes, potentially due to biological differences in the cellular expression and regulation of these targets. Here, we review current clinical data on combination immune checkpoint inhibitor therapy in metastatic kidney cancer and discuss the relevant biology of PD-1 and PD-L1. The design of future rational combination therapy trials in metastatic renal cell carcinoma will rely upon an understanding of this biology, along with an evolving understanding of immune cell populations and their functional states in the tumor microenvironment.

中文翻译：

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在转移性肾癌中靶向PD-1或PD-L1：在一线治疗中的联合治疗。

FDA最近针对靶向程序性死亡1（PD-1）的方案与抗CTLA-4或VEGF酪氨酸激酶抑制剂组合的批准正在重塑转移性肾癌的一线治疗方法。同时，对程序性死亡配体1（PD-L1）（PD-1的两个主要配体之一）具有特异性的疗法仍在继续研究中。出人意料的是，并非所有的PD-1和PD-L1药物都能导致相似的临床结果，这可能是由于这些靶标在细胞表达和调控方面的生物学差异所致。在这里，我们审查了转移性肾癌联合免疫检查点抑制剂治疗的当前临床数据，并讨论了PD-1和PD-L1的相关生物学。将来在转移性肾细胞癌中进行合理的联合治疗试验的设计将取决于对这种生物学的理解，