PD-1/PD-L1-checkpoint blockade therapy is generally thought to relieve tumor cell-mediated suppression in the tumor microenvironment but PD-L1 is also expressed on non-tumor macrophages and conventional dendritic cells (cDCs). Here we show in mouse tumor models that tumor-draining lymph nodes (TDLNs) are enriched for tumor-specific PD-1⁺ T cells which closely associate with PD-L1⁺ cDCs. TDLN-targeted PD-L1-blockade induces enhanced anti-tumor T cell immunity by seeding the tumor site with progenitor-exhausted T cells, resulting in improved tumor control. Moreover, we show that abundant PD-1/PD-L1-interactions in TDLNs of nonmetastatic melanoma patients, but not those in corresponding tumors, associate with early distant disease recurrence. These findings point at a critical role for PD-L1 expression in TDLNs in governing systemic anti-tumor immunity, identifying high-risk patient groups amendable to adjuvant PD-1/PD-L1-blockade therapy.

通常认为PD-1 / PD-L1-检查点阻断疗法可减轻肿瘤微环境中肿瘤细胞介导的抑制作用，但PD-L1也可在非肿瘤巨噬细胞和常规树突状细胞（cDC）上表达。在这里，我们在小鼠肿瘤模型中显示，引流淋巴结（TDLN）富含与PD-L1 ⁺密切相关的肿瘤特异性PD-1 ⁺ T细胞cDC。TDLN靶向的PD-L1阻滞剂通过在祖细胞耗尽的T细胞上播种肿瘤部位，从而增强了抗肿瘤T细胞免疫力，从而改善了肿瘤控制。此外，我们发现非转移性黑色素瘤患者的TDLNs中有大量PD-1 / PD-L1相互作用，而相应肿瘤中的PD-1 / PD-L1相互作用与早期远处复发有关。这些发现指出了PD-L1在TDLNs中的表达在控制全身性抗肿瘤免疫力中的关键作用，从而确定了可通过辅助性PD-1 / PD-L1阻断疗法进行治疗的高危患者群体。