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PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung
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 ampli...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360842/ https://www.ncbi.nlm.nih.gov/pubmed/33576873 http://dx.doi.org/10.1007/s00262-020-02825-z |
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author | Goldmann, Torsten Marwitz, Sebastian Nitschkowski, Dörte Krupar, Rosemarie Backman, Max Elfving, Hedvig Thurfjell, Viktoria Lindberg, Amanda Brunnström, Hans La Fleur, Linnea Mezheyeuski, Artur Mattsson, Johanna Sofia Margareta Botling, Johan Micke, Patrick Strell, Carina |
author_facet | Goldmann, Torsten Marwitz, Sebastian Nitschkowski, Dörte Krupar, Rosemarie Backman, Max Elfving, Hedvig Thurfjell, Viktoria Lindberg, Amanda Brunnström, Hans La Fleur, Linnea Mezheyeuski, Artur Mattsson, Johanna Sofia Margareta Botling, Johan Micke, Patrick Strell, Carina |
author_sort | Goldmann, Torsten |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-020-02825-z. |
format | Online Article Text |
id | pubmed-8360842 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-83608422021-08-30 PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung Goldmann, Torsten Marwitz, Sebastian Nitschkowski, Dörte Krupar, Rosemarie Backman, Max Elfving, Hedvig Thurfjell, Viktoria Lindberg, Amanda Brunnström, Hans La Fleur, Linnea Mezheyeuski, Artur Mattsson, Johanna Sofia Margareta Botling, Johan Micke, Patrick Strell, Carina Cancer Immunol Immunother Original Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-020-02825-z. Springer Berlin Heidelberg 2021-02-12 2021 /pmc/articles/PMC8360842/ /pubmed/33576873 http://dx.doi.org/10.1007/s00262-020-02825-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Goldmann, Torsten Marwitz, Sebastian Nitschkowski, Dörte Krupar, Rosemarie Backman, Max Elfving, Hedvig Thurfjell, Viktoria Lindberg, Amanda Brunnström, Hans La Fleur, Linnea Mezheyeuski, Artur Mattsson, Johanna Sofia Margareta Botling, Johan Micke, Patrick Strell, Carina PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung |
title | PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung |
title_full | PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung |
title_fullStr | PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung |
title_full_unstemmed | PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung |
title_short | PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung |
title_sort | pd-l1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360842/ https://www.ncbi.nlm.nih.gov/pubmed/33576873 http://dx.doi.org/10.1007/s00262-020-02825-z |
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