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 SalihOliver Borst, Hans Georg Kopp, Lars Zender

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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.

Original languageEnglish
Article number7005
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - Dec 2021
Externally publishedYes

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