POLE Score: a comprehensive profiling of programmed death 1 ligand 1 expression in pancreatic ductal adenocarcinoma
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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
Susanne Sebens, email: [email protected]
Keywords: PD-L1; pancreatic cancer; tumor stroma; prognostic relevance
Received: March 20, 2018 Accepted: January 19, 2019 Published: February 22, 2019
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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