Oncotarget

Research Papers:

PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma

Tim Müller, Martin Braun, Dimo Dietrich, Seher Aktekin, Simon Höft, Glen Kristiansen, Friederike Göke, Andreas Schröck, Johannes Brägelmann, Stefanie A.E. Held, Friedrich Bootz and Peter Brossart _

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Oncotarget. 2017; 8:52889-52900. https://doi.org/10.18632/oncotarget.17547

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Abstract

Tim Müller1,*, Martin Braun1,*, Dimo Dietrich1, Seher Aktekin1, Simon Höft1, Glen Kristiansen1, Friederike Göke2, Andreas Schröck2, Johannes Brägelmann3, Stefanie A.E. Held3, Friedrich Bootz2,* and Peter Brossart3,*

1Institute of Pathology, University Hospital Bonn, Bonn, Germany

2Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital Bonn, Bonn, Germany

3Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany

*These authors have contributed equally to this work

Correspondence to:

Peter Brossart, email: Peter.Brossart@ukb.uni-bonn.de

Keywords: PD-L1, prognostic biomarker, head and neck squamous cell carcinoma, immunohistochemistry

Received: December 14, 2016    Accepted: March 17, 2017    Published: May 02, 2017

ABSTRACT

Background: The PD-1 receptor and its ligands PD-L1 and PD-L2 are known to be significantly involved in T-cell regulation. Recent studies suggest that PD-L1 expression in malignant tumors contributes to an immunosuppressive microenvironment and disruption of antitumoral immune response. Drugs targeting this pathway are already tested in clinical trials against several tumor entities with promising results. However, until now comprehensive data with regard to PD-L1 and PD-L2 expression in head and neck squamous cell carcinoma (HNSCC) is still lacking.

Patients and methods: We assessed PD-L1 and PD-L2 expression via immunohistochemistry in two independent cohorts of 293 HNSCC patients.

Results: A significant subset of HNSCC showed high expression levels of PD-L1. Most remarkable, we detected a strong correlation between PD-L1 expression and overall survival time in both HNSCC cohorts. Further, in multivariate cox proportional hazard models, PD-L1 dominates as the strongest prognostic factor of patient’s outcome in HNSCC, leaving even tumor stage and distant metastasis behind. Moreover, strong PD-L1 expression was associated with the presence of distant metastases in a subset of cases.

Conclusions: In summary, while the significance of PD-L2 in HNSCC seems to minor, we show that PD-L1 expression is common in HNSCC and, more importantly, a both robust and strong prognostic biomarker. In this respect, our results provide hints on further application of therapies targeting the PD-1/PD-L1 pathway in HNSCC. Investigation of response and outcome of patients receiving anti-PD-1/PD-L1 containing therapies in correlation with PD-L1 expression analysis should be an important task for the future.

STATEMENT OF TRANSLATIONAL RELEVANCE

In spite of improved treatment options and increasing knowledge of molecular alterations in HNSCC, the survival rate has not been dramatically changed in the past decades. Pies are missing in HNSCC. One promising candidate in cancer immune therapy is PD-L1.

Drugs targeting PD-L1 or its receptor PD-1 are subject of several clinical studies in different cancer entities. However, comprehensive data about PD-L1 expression in HNSCC and therefore a rational basis for anti PD-L1/PD-1 therapy in HNSCC is lacking. Here, we provide wide-ranging data about PD-L1 expression in HNSCC of all major localizations. We observed a strong correlation between expression of PD-L1 and reduced overall survival time. Furthermore, high PD-L1 expression was identified as a strong prognostic factor of patient’s outcome when verified together with recognized prognostic factors.


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