Platelet PD-L1 reflects collective intratumoral PD-L1 expression and predicts immunotherapy response in non-small cell lung cancer

The definition of biomarkers to predict therapy responses to immune-checkpoint inhibitors represent an unmet clinical need. Here the authors provide evidences that platelet-derived PD-L1 could serve as a prognostic and predictive biomarker in patients with non-small cell lung cancer. 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 alpha 5 beta 1 and GPIb alpha-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.

Automated summary

This study demonstrates that platelet-derived PD-L1 can serve as a prognostic and predictive biomarker in non-small cell lung cancer patients, playing a role in tumor immune evasion and affecting T cell function. An algorithm was developed to calculate the adjusted PD-L1 payload of platelets (pPD-L1(Adj.)), which showed superior predictive ability for therapy response compared to standard histological PD-L1 quantification.