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Oncoimmunology. 2016 Mar 16;5(5):e1131379. doi: 10.1080/2162402X.2015.1131379. eCollection 2016 May.

PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations.

Author information

1
Institute of Pathology, University Hospital Cologne , Cologne, Germany.
2
Center for Integrated Oncology Köln Bonn, Cologne, Germany; Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
3
Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne , Cologne, Germany.
4
Department of Translational Genomics, Medical Faculty, University of Cologne , Cologne, Germany.
5
Department of Pathology, Hospital Merheim , Cologne, Germany.
6
Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH , Cologne, Germany.
7
University of Groningen and University Medical Center, Department of Pulmonary Diseases , Groningen, Netherlands.
8
Department of Pathology, University of Groningen and University Medical Center Groningen , Groningen, Netherlands.
9
Pathology Network of the University Hospital of Luebeck and Leibniz Research Center Borstel , Luebeck and Borstel, Germany.

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.

KEYWORDS:

5H1; Checkpoint inhibition; PD-L1; early stage NSCLC; genetic alterations; immunohistochemistry; non-small cell lung cancer

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