PD-L1/PD-1 blocking antibodies have demonstrated therapeutic efficacy across a range of human cancers. Extending this benefit to a greater number of patients, however, will require a better understanding of how these therapies instigate anticancer immunity. Although the PD-L1/PD-1 axis is typically associated with T cell function, we demonstrate here that dendritic cells (DCs) are an important target of PD-L1 blocking antibody. PD-L1 binds two receptors, PD-1 and B7.1 (CD80). PD-L1 is expressed much more abundantly than B7.1 on peripheral and tumor-associated DCs in patients with cancer. Blocking PD-L1 on DCs relieves B7.1 sequestration in cis by PD-L1, which allows the B7.1/CD28 interaction to enhance T cell priming. In line with this, in patients with renal cell carcinoma or non–small cell lung cancer treated with atezolizumab (PD-L1 blockade), a DC gene signature is strongly associated with improved overall survival. These data suggest that PD-L1 blockade reinvigorates DC function to generate potent anticancer T cell immunity.

PD-L1/PD-1 阻断抗体已在一系列人类癌症中显示出治疗效果。然而，将这种益处扩展到更多的患者需要更好地了解这些疗法如何激发抗癌免疫。尽管 PD-L1/PD-1 轴通常与 T 细胞功能相关，但我们在此证明树突状细胞 (DC) 是 PD-L1 阻断抗体的重要靶标。PD-L1 结合两种受体，PD-1 和 B7.1 (CD80)。在癌症患者的外周和肿瘤相关 DCs 上，PD-L1 比 B7.1 更丰富地表达。阻断 DCs 上的 PD-L1 可减轻 PD-L1 在顺式中的 B7.1 隔离，从而使 B7.1/CD28 相互作用增强 T 细胞启动。与此一致，在接受atezolizumab（PD-L1阻断剂）治疗的肾细胞癌或非小细胞肺癌患者中，DC 基因特征与改善的总体存活率密切相关。这些数据表明，PD-L1 阻断可重振 DC 功能以产生有效的抗癌 T 细胞免疫。