Universität zu Köln

Scheel, Andreas H., Ansen, Sascha, Schultheis, Anne M., Scheffler, Matthias ORCID: 0000-0002-9031-1368, Fischer, Rieke N., Michels, Sebastian, Hellmich, Martin, George, Julie, Zander, Thomas, Brockmann, Michael, Stoelben, Erich, Groen, Harry, Timens, Wim ORCID: 0000-0002-4146-6363, Perner, Sven, von Bergwelt-Baildon, Michael, Buettner, Reinhard and Wolf, Juergen (2016). PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations. OncoImmunology, 5 (5). PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 2162-402X

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Scheel, Andreas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ansen, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultheis, Anne M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheffler, Matthias UNSPECIFIED orcid.org/0000-0002-9031-1368 UNSPECIFIED Fischer, Rieke N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Michels, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hellmich, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED George, Julie UNSPECIFIED UNSPECIFIED UNSPECIFIED Zander, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Brockmann, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoelben, Erich UNSPECIFIED UNSPECIFIED UNSPECIFIED Groen, Harry UNSPECIFIED UNSPECIFIED UNSPECIFIED Timens, Wim UNSPECIFIED orcid.org/0000-0002-4146-6363 UNSPECIFIED Perner, Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED von Bergwelt-Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-293228
DOI:	10.1080/2162402X.2015.1131379
Journal or Publication Title:	OncoImmunology
Volume:	5
Number:	5
Date:	2016
Publisher:	TAYLOR & FRANCIS INC
Place of Publication:	PHILADELPHIA
ISSN:	2162-402X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEATH-LIGAND 1; NIVOLUMAB; IMMUNE; TUMOR; ANTIBODY; B7-H1; ADENOCARCINOMA; PEMBROLIZUMAB; AMPLIFICATION; CHEMOTHERAPY Multiple languages Oncology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29322