PD-L1 expression in non-small cell lung cancer: correlations with genetic alterations
Open accessAbstract
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.
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Co-mutations of KRAS and TP53 are correlated with expression of PD-L1 in NSCLC.
“Further therapeutic considerations might arise from the finding that co-mutations of KRAS and tumor protein p53 gene (TP53) are correlated with expression of programmed death ligand 1 in NSCLC, 27,28 suggesting that these tumors might be predictive for antiprogrammed death 1/programmed death ligand 1 immunotherapy.”
From K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways (2019) · cites this paper as [27]
KEAP1-inactivating mutations have been linked to changes in the NSCLC immune microenvironment.
“Inactivating mutations in KEAP1 have also been associated with an altered NSCLC immune microenvironment134.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [134]
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- Authors
- Scheel, A. H., Ansén, S., Schultheis, A. M., Scheffler, M., Fischer, R. N., Michels, S., Hellmich, M., George, J., Zander, T., Brockmann, M., Stoelben, E., Groen, H., Timens, W., Perner, S., von Bergwelt-Baildon, M., Büttner, R., & Wolf, J.
- Affiliations
- University Hospital Cologne (DE)
- University of Cologne (DE)
- Kliniken der Stadt Köln (DE)
- University Medical Center Groningen (NL)
- Research Center Borstel - Leibniz Lung Center (DE)
- Corresponding author
- Scheel, Andreas H.
- Ansén, Sascha
- ORCID
- Venue
- OncoImmunology
- Publisher
- Informa UK Limited
- Published
- 2016-03-16
- Volume
- 5
- Issue
- 5
- Pages
- e1131379
- ISSN
- 2162-4011 (ISSN-L)
- 2162-402X
- PMC
- PMC4910698
- OpenAlex
- W2323356988
- Cited by
- 111
- References
- 41
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 14 · 2021: 16 · 2020: 16 · 2019: 13 · 2018: 21 · 2017: 14
- FWCI
- 8.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- OncoImmunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Universität zu Köln
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- PD-L1 expression, non-small cell lung cancer, TP53 mutation, KRAS mutation, STK11 mutation, NFE2L2 mutation, tumor-infiltrating immune cells, tumor mutational burden, smoking, predictive biomarkers, anti-PD-1 therapy, early-stage lung cancer, adenocarcinoma, squamous cell carcinoma, neoantigens
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