Evidence map›Paper›PMID 33576873›Full record

ArticleCancer immunology, immunotherapy : CII2021

PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung.

Torsten Goldmann, Sebastian Marwitz, Dörte Nitschkowski, Rosemarie Krupar, Max Backman, Hedvig Elfving, Viktoria Thurfjell, Amanda Lindberg, Hans Brunnström, Linnea La Fleur and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.6field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
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  3. Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025
    Review
  4. Current oncology (Toronto, Ont.) · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

Torsten GoldmannDivision of Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Sebastian MarwitzDivision of Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Dörte NitschkowskiDivision of Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Rosemarie KruparDivision of Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.
Max BackmanDepartment of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Hedvig ElfvingDepartment of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Viktoria ThurfjellDepartment of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Amanda LindbergDepartment of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Hans BrunnströmDivision of Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
Linnea La FleurDepartment of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Artur MezheyeuskiDepartment of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Johanna Sofia Margareta MattssonDepartment of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Johan BotlingDepartment of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Patrick Micke *Department of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
Carina Strell *Department of Immunology, Genetics, and Pathology, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden. carina.strell@igp.uu.se.ORCID http://orcid.org/0000-0002-3783-7256
Uppsala University · SEResearch Center Borstel - Leibniz Lung Center · DELund University · SEUniversity Hospital Schleswig-Holstein · DE

Funding

Deutsche Zentrum für Lungenforschung DZL;82DZL001A5Radiumhemmets Forskningsfonder rafo 174292
6 · The paper itself

Abstract

Gene amplification is considered to be one responsible cause for upregulation of Programmed Death Ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) and to represent a specific molecular subgroup possibly associated with immunotherapy response. Our aim was to analyze the frequency of PD-L1 amplification, its relation to PD-L1 mRNA and protein expression, and to characterize the immune microenvironment of amplified cases. The study was based on two independent NSCLC cohorts, including 354 and 349 cases, respectively. Tissue microarrays were used to evaluate PD-L1 amplification by FISH and PD-L1 protein by immunohistochemistry. Immune infiltrates were characterized immunohistochemically by a panel of immune markers (CD3, CD4, CD8, PD-1, Foxp3, CD20, CD138, CD168, CD45RO, NKp46). Mutational status was determined by targeted sequencing. RNAseq data was available for 197 patients. PD-L1 amplification was detected in 4.5% of all evaluable cases. PD-L1 amplification correlated only weakly with mRNA and protein expression. About  37% of amplified cases were negative for PD-L1 protein. PD-L1 amplification did not show any association with the mutational status. In squamous cell cancer, PD-L1 amplified cases were enriched among patients with high tumoral immune cell infiltration and showed gene expression profiles related to immune exhaustion. In conclusion, PD-L1 amplification correlates with PD-L1 expression in squamous cell cancer and was associated with an immune cell rich tumor phenotype. The correlative findings help to understand the role of PD-L1 amplification as an important immune escape mechanism in NSCLC and suggest the need to further evaluate PD-L1 amplification as predictive biomarker for checkpoint inhibitor therapy.

Indexed as

Gene AmplificationB7-H1 AntigenBiomarkers, TumorCarcinoma, Squamous CellComputational BiologyGene ExpressionGene FrequencyHumansImmunohistochemistryImmunophenotypingIn Situ Hybridization, FluorescenceLung NeoplasmsLymphocytes, Tumor-InfiltratingMutationPhenotypeTissue Array AnalysisB7-H1 AntigenBiomarkers, TumorCD274 protein, humanCheck-point inhibitorsImmunotherapyLung cancerMicroenvironmentPD-L1 amplification

Identifiers

PMID33576873
PMCPMC8360842
OpenAlexW3126772227

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.