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

Clemens Hinterleitner, Jasmin Strähle, Elke Malenke, Martina Hinterleitner, Melanie Henning, Marco Seehawer, Tatjana Bilich, Jonas Heitmann, Martina Lutz, Sven Mattern, Sophia Scheuermann, Marius Horger, Stefanie Maurer, Juliane Walz, Falko Fend, Rupert Handgretinger, Christian Seitz, Bettina Weigelin, Stephan Singer, Helmut Salih, Oliver Borst, Hans-Georg Kopp and Lars Zender ()
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Clemens Hinterleitner: University Hospital Tuebingen
Jasmin Strähle: University Hospital Tuebingen
Elke Malenke: University Hospital Tuebingen
Martina Hinterleitner: University Hospital Tuebingen
Melanie Henning: University Hospital Tuebingen
Marco Seehawer: University Hospital Tuebingen
Tatjana Bilich: University of Tuebingen
Jonas Heitmann: University of Tuebingen
Martina Lutz: University of Tuebingen
Sven Mattern: University Hospital Tuebingen
Sophia Scheuermann: University of Tuebingen
Marius Horger: University Hospital Tuebingen
Stefanie Maurer: University of Tuebingen
Juliane Walz: University of Tuebingen
Falko Fend: University Hospital Tuebingen
Rupert Handgretinger: University of Tuebingen
Christian Seitz: University of Tuebingen
Bettina Weigelin: Eberhard Karls University Tuebingen
Stephan Singer: University Hospital Tuebingen
Helmut Salih: University of Tuebingen
Oliver Borst: University Hospital, Department of Cardiology and Angiology, Eberhard Karls University of Tuebingen
Hans-Georg Kopp: Robert-Bosch-Hospital, Department of Molecular and Pneumological Oncology
Lars Zender: University Hospital Tuebingen

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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-L1Adj.), 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.

Date: 2021
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DOI: 10.1038/s41467-021-27303-7

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