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PD-L1 amplification...
PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung
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- Goldmann, Torsten (author)
- Leibniz Lung Ctr, Res Ctr Borstel, Div Pathol, Borstel, Germany.;German Ctr Lung Res DZL, Airway Res Ctr North ARCN, Grosshansdorf, Germany.,Research Center Borstel,Forschungszentrum Borstel - Zentrum für Medizin und Biowissenschaften
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- Marwitz, Sebastian (author)
- Leibniz Lung Ctr, Res Ctr Borstel, Div Pathol, Borstel, Germany.;German Ctr Lung Res DZL, Airway Res Ctr North ARCN, Grosshansdorf, Germany.,Forschungszentrum Borstel - Zentrum für Medizin und Biowissenschaften,Research Center Borstel
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- Nitschkowski, Dorte (author)
- Leibniz Lung Ctr, Res Ctr Borstel, Div Pathol, Borstel, Germany.;German Ctr Lung Res DZL, Airway Res Ctr North ARCN, Grosshansdorf, Germany.,Research Center Borstel,Forschungszentrum Borstel - Zentrum für Medizin und Biowissenschaften
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- Krupar, Rosemarie (author)
- Leibniz Lung Ctr, Res Ctr Borstel, Div Pathol, Borstel, Germany.;Univ Hosp Schleswig Holstein, Inst Pathol, Campus Lubeck, Lubeck, Germany.,University Medical Center Schleswig-Holstein,Research Center Borstel
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- Backman, Max (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Elfving, Hedvig (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Thurfjell, Viktoria (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi
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- Lindberg, Amanda (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi
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- Brunnström, Hans (author)
- Lund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Region Skåne,Lund Univ, Dept Clin Sci Lund, Div Pathol, Lund, Sweden.;Reg Skane, Dept Genet & Pathol, Div Lab Med, Lund, Sweden.
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- La Fleur, Linnea (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Johan Botling
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- Mezheyeuski, Artur (author)
- Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi
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- Mattsson, Johanna Sofia Margareta, 1985- (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Botling, Johan (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Johan Botling
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- Micke, Patrick (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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- Strell, Carina (author)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke
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Leibniz Lung Ctr, Res Ctr Borstel, Div Pathol, Borstel, Germany;German Ctr Lung Res DZL, Airway Res Ctr North ARCN, Grosshansdorf, Germany. Research Center Borstel (creator_code:org_t)
- 2021-02-12
- 2021
- English.
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In: Cancer Immunology and Immunotherapy. - : Springer Nature. - 0340-7004 .- 1432-0851. ; 70:9, s. 2577-2587
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- Check-point inhibitors
- Lung cancer
- Microenvironment
- Immunotherapy
- PD-L1 amplification
- Pathology
- Patologi
- Check-point inhibitors
- Immunotherapy
- Lung cancer
- Microenvironment
- PD-L1 amplification
Publication and Content Type
- ref (subject category)
- art (subject category)
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Goldmann, Torste ...
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Marwitz, Sebasti ...
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Nitschkowski, Do ...
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Krupar, Rosemari ...
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Backman, Max
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Elfving, Hedvig
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Thurfjell, Vikto ...
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Lindberg, Amanda
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Brunnström, Hans
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La Fleur, Linnea
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Mezheyeuski, Art ...
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Mattsson, Johann ...
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Botling, Johan
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Micke, Patrick
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Strell, Carina
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
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Cancer Immunolog ...
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Uppsala University
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Lund University