Oncotarget

Research Papers:

PD-L1 is expressed on human platelets and is affected by immune checkpoint therapy

Verena Rolfes, Christian Idel, Ralph Pries, Kirstin Plötze-Martin, Jens Habermann, Timo Gemoll, Sabine Bohnet, Eicke Latz, Julika Ribbat-Idel, Bernardo S. Franklin and Barbara Wollenberg _

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Oncotarget. 2018; 9:27460-27470. https://doi.org/10.18632/oncotarget.25446

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Abstract

Verena Rolfes1,*, Christian Idel2,*, Ralph Pries2,*, Kirstin Plötze-Martin2, Jens Habermann3, Timo Gemoll3, Sabine Bohnet4, Eicke Latz1,5,6, Julika Ribbat-Idel7, Bernardo S. Franklin1,* and Barbara Wollenberg2,*

1Institute of Innate Immunity, University Hospital, University of Bonn, Bonn, Germany

2University Hospital Schleswig Holstein, Campus Lübeck, Clinic for Otorhinolaryngology – Head and Neck Surgery, Luebeck, Germany

3University Hospital Schleswig Holstein, Campus Lübeck, Section for Translational Oncology and Biobanking, Clinic for Surgery, Luebeck, Germany

4University Hospital Schleswig Holstein, Campus Lübeck, Clinic for Pulmonary Medicine, Luebeck, Germany

5Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA

6German Center for Neurodegenerative Diseases, Bonn, Germany

7Department 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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