PD-L1 is expressed on human platelets and is affected by immune checkpoint therapy
2018
// Verena Rolfes 1, * , Christian Idel 2, * , Ralph Pries 2, * , Kirstin Plotze-Martin 2 , Jens Habermann 3 , Timo Gemoll 3 , Sabine Bohnet 4 , Eicke Latz 1, 5, 6 , Julika Ribbat-Idel 7 , Bernardo S. Franklin 1, * and Barbara Wollenberg 2, * 1 Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany 2 University Hospital Schleswig Holstein, Campus Lubeck, Clinic for Otorhinolaryngology – Head and Neck Surgery, Luebeck, Germany 3 University Hospital Schleswig Holstein, Campus Lubeck, Section for Translational Oncology and Biobanking, Clinic for Surgery, Luebeck, Germany 4 University Hospital Schleswig Holstein, Campus Lubeck, Clinic for Pulmonary Medicine, Luebeck, Germany 5 Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA 6 German Center for Neurodegenerative Diseases, Bonn, Germany 7 Department of Pathology, University Medical Center Schleswig-Holstein, Luebeck, Germany * These authors have contributed equally to this work Correspondence to: Barbara Wollenberg, email: Barbara.Wollenberg@uksh.de Bernardo S. Franklin, email: franklin@uni-bonn.de Keywords: head and neck cancer; biomarkers for PD1-PD-L1 checkpoint therapy; tumor-educated platelets; atezolizumab Received: March 07, 2018 Accepted: April 28, 2018 Published: June 08, 2018 ABSTRACT Cancer immunotherapy has been revolutionised by drugs that enhance the ability of the immune system to detect and fight tumors. Immune checkpoint therapies that target the programmed death-1 receptor (PD-1), or its ligand (PD-L1) have shown unprecedented rates of durable clinical responses in patients with various cancer types. However, there is still a large fraction of patients that do not respond to checkpoint inhibitors, and the challenge remains to find cellular and molecular cues that could predict which patients would benefit from these therapies. Using a series of qualitative and quantitative methods we show here that PBMCs and platelets from smokers and patients with head and neck squamous cell carcinoma (HNSCC) or lung cancer express and up-regulate PD-L1 independently of tumor stage. Furthermore, treatment with Atezolizumab, a fully humanised monoclonal antibody against PD-L1, in 4 patients with lung cancer caused a decrease in PD-L1 expression in platelets, which was restored over 20 days. Altogether, our findings reveal the expression of the main therapeutic target in current checkpoint therapies in human platelets and highlight their potential as biomarkers to predict successful therapeutic outcomes.
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