Oncotarget

Research Papers:

POLE Score: a comprehensive profiling of programmed death 1 ligand 1 expression in pancreatic ductal adenocarcinoma

Sascha Rahn, Sandra Krüger, Ruben Mennrich, Lisa Goebel, Daniela Wesch, Hans-Heinrich Oberg, Ilka Vogel, Michael Ebsen, Christoph Röcken, Ole Helm and Susanne Sebens _

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Oncotarget. 2019; 10:1572-1588. https://doi.org/10.18632/oncotarget.26705

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Abstract

Sascha Rahn1, Sandra Krüger2, Ruben Mennrich1, Lisa Goebel1, Daniela Wesch3, Hans-Heinrich Oberg3, Ilka Vogel4, Michael Ebsen5, Christoph Röcken2, Ole Helm1,* and Susanne Sebens1,*

1Institute for Experimental Cancer Research, Christian-Albrechts-University Kiel (CAU) and University Medical Center Schleswig-Holstein (UK-SH), Campus Kiel, Kiel, Germany

2Department of Pathology, CAU and UK-SH, Campus Kiel, Kiel, Germany

3Institute of Immunology, CAU and UK-SH, Campus Kiel, Kiel, Germany

4Department of Surgery, Community Hospital Kiel, Kiel, Germany

5Institute of Pathology, Community Hospital Kiel, Kiel, Germany

*Shared senior authorship

Correspondence to:

Susanne Sebens, email: susanne.sebens@email.uni-kiel.de

Keywords: PD-L1; pancreatic cancer; tumor stroma; prognostic relevance

Received: March 20, 2018     Accepted: January 19, 2019     Published: February 22, 2019

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) being characterized by a pronounced stromal compartment is commonly diagnosed at an advanced stage limiting curative treatment options. Although therapeutical targeting of immune checkpoint regulators like programmed death 1 ligand 1 (PD-L1) represent a promising approach that substantially improved survival of several highly aggressive malignancies, convincing indicators for response prediction are still lacking for PDAC which might be attributed to the insufficient characterization of PD-L1 status. Therefore, we investigated PD-L1 expression by immunohistochemistry in a well characterized cohort of 59 PDAC and 18 peritumoral tissues. Despite the histopathological homogeneity within our cohort, tumor tissues exhibited a great heterogeneity regarding PD-L1 expression. Considering distinct PD-L1 expression patterns, we established the novel POLE Score that incorporates overall PD-L1 expression (P), cellular Origin of PD-L1 (O), PD-L1 level in tumor-associated Lymph follicles (L) and Enumerated local PD-L1 distribution (E). We show that tumoral PD-L1 expression is higher compared to peritumoral areas. Furthermore, POLE Score parameters correlated with overall survival, tumor grade, Ki67 status, local proximity of tumor cells and particular stroma composition. For the first time, we demonstrate that PD-L1 is mostly expressed by stroma and rarely by tumor cells in PDAC. Moreover, our in situ analyses on serial tissue sections and in vitro data suggest that PD-L1 is prominently expressed by tumor-associated macrophages. In conclusion, POLE Score represents a comprehensive characterization of PD-L1 expression in tumor and stroma compartment and might provide the basis for improved patient stratification in future clinical trials on PD-1/PD-L1 targeting therapies in PDAC.


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