Platelet Programmed Cell Death Ligand 1 (pPDL-1) Is a Prognostic Marker in Advanced Lung Cancer

Introduction. PDL-1 (Programmed Cell Death Ligand-1) expressed on non small cell lung cancer (NSCLC) cells mediates immune escape, and inhibition of PDL-1/PD-1 interaction with blocking antiboides induces long-term responses in a subpopulation of patients with metastatic NSCLC. PDL-1 immunohistochemistry is a controversial means of predicting responders, and further biomarkers are urgently needed. Herein, we report on the phenomenon of PDL-1 expressed on the surface of platelets (platelet PDL-1, pPDL-1) in patients with advanced NSCLC.

Methods. Blood samples were prospectively collected from patients, and platelet-expressed PDL-1 expression was measured by flow cytometry utilizing flow monoclonal antibodies clones MIH1 and 28-8. Correlations of pPDL-1 expression levels with histopathological data, laboratory data, and survival were analyzed.

Results. 79 NSCLC patients (53 with adenocarcinoma and 26 with squamous cell carcinoma) and 42 healthy controls were analyzed. 61 patients (77.2%) had stage IV disease. Platelets derived from healthy controls expressed little if any pPDL-1. Mean pPDL-1 expression in tumor patients was significantly increased compared with controls. PPDL-1 was not correlated with histological subtypes, mutational status, smoking history, clinical stage or laboratory data. However, overall survival (OS) and progression free survival (PFS) were significantly reduced in patients with a high (above median) percentage of PDL-1-positive platelets as compared with low pPDL-1(OS: 29 vs. 45 months, p = 0.027, PFS: 6 vs. 9 months, p = 0.036). The accuracy of our system was validated by calculating the area under the receiver-operator characteristic (ROC) curve. Here, platelet-derived PDL-1 expression was also significantly associated with a reduced OS (AUC=0.719, 95 CI: 0.587- 0.851) and PFS (AUC=0.768, 95 CI: 0.59- 0.89).

Conclusion. To our knowledge, this is the first report of PDL-1 expression on platelets. In NSCLC patients, high pPDL-1 - similar to tumor PDL-1 - is clearly prognostic. The functional significance and predictive value of pPDL-1 remains to be established.