Immune-checkpoint inhibitors (ICI) have transformed oncological therapy. Up to 20% of all non-small cell lung cancers (NSCLCs) show durable responses upon treatment with ICI, however, robust markers to predict therapy response are missing. Here we show that blood platelets interact with lung cancer cells and that PD-L1 protein is transferred from tumor cells to platelets in a fibronectin 1, integrin α5β1 and GPIbα-dependent manner. Platelets from NSCLC patients are found to express PD-L1 and platelet PD-L1 possess the ability to inhibit CD4 and CD8 T-cells. An algorithm is developed to calculate the activation independent adjusted PD-L1 payload of platelets (pPD-L1^Adj.), which is found to be superior in predicting the response towards ICI as compared to standard histological PD-L1 quantification on tumor biopsies. Our data suggest that platelet PD-L1 reflects the collective tumor PD-L1 expression, plays important roles in tumor immune evasion and overcomes limitations of histological quantification of often heterogeneous intratumoral PD-L1 expression.

免疫检查点抑制剂 (ICI) 已经改变了肿瘤治疗。高达 20% 的非小细胞肺癌 (NSCLC) 在接受 ICI 治疗后表现出持久的反应，但是，缺少预测治疗反应的有力标志物。在这里，我们显示血小板与肺癌细胞相互作用，PD-L1 蛋白以纤连蛋白 1、整合素 α5β1 和 GPIbα 依赖性方式从肿瘤细胞转移到血小板。NSCLC 患者的血小板被发现表达 PD-L1，血小板 PD-L1 具有抑制 CD4 和 CD8 T 细胞的能力。开发了一种算法来计算血小板的激活独立调整 PD-L1 有效负载 (pPD-L1 ^Adj.)，与肿瘤活检的标准组织学 PD-L1 量化相比，它被发现在预测对 ICI 的反应方面更优越。我们的数据表明，血小板 PD-L1 反映了集体肿瘤 PD-L1 表达，在肿瘤免疫逃逸中起着重要作用，并克服了通常异质性肿瘤内 PD-L1 表达的组织学定量限制。