title: PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations.
abstract: Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and association with genetically defined subtypes have not been addressed systematically. Here, we analyzed PD-L1 expression in 436 genetically annotated NSCLC specimens enriched for early stages using PD-L1 antibody 5H1. Expression of PD-L1 was detected in the tumor cells (TC) (34% of cases) and in associated immune cells (IC) (49%) across all stages of NSCLC, either alone or in combination. PD-L1 IHC-positive TC, but not IC showed significantly higher PD-L1 RNA expression levels. Expression in TC was associated with TP53, KRAS and STK11 mutational status in adenocarcinomas (AD) and with NFE2L2 mutations in squamous cell carcinomas (SQ). No correlations with histological subtype, clinical characteristics and overall survival were found. The presence of PD-L1-positive IC was significantly associated with patients' smoking status in AD. The findings are in agreement with the emerging concept that tumors with high mutational burden are more likely to benefit from immunotherapy, since TP53 and KRAS mutations are linked to smoking, increased numbers of somatic mutations and expression of neoantigens. Current clinical studies focus on stage IIIB and IV NSCLC; however, PD-L1 expression occurs in earlier stages and might be a predictive biomarker in clinical trials testing (neo-) adjuvant strategies.
authors.affiliation: Institute of Pathology, University Hospital Cologne , Cologne, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Scheel
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Ansén
authors.affiliation: Institute of Pathology, University Hospital Cologne , Cologne, Germany.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Schultheis
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Scheffler
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Rieke N
authors.initials: RN
authors.lastname: Fischer
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Michels
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne , Cologne, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hellmich
authors.affiliation: Department of Translational Genomics, Medical Faculty, University of Cologne , Cologne, Germany.
authors.forename: Julie
authors.initials: J
authors.lastname: George
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Zander
authors.affiliation: Department of Pathology, Hospital Merheim , Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Brockmann
authors.affiliation: Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH , Cologne, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Stoelben
authors.affiliation: University of Groningen and University Medical Center, Department of Pulmonary Diseases , Groningen, Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Groen
authors.affiliation: Department of Pathology, University of Groningen and University Medical Center Groningen , Groningen, Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: Pathology Network of the University Hospital of Luebeck and Leibniz Research Center Borstel , Luebeck and Borstel, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: von Bergwelt-Baildon
authors.affiliation: Institute of Pathology, University Hospital Cologne , Cologne, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Büttner
authors.affiliation: Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wolf
keywords: 5H1; Checkpoint inhibition; PD-L1; early stage NSCLC; genetic alterations; immunohistochemistry; non-small cell lung cancer