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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 LU orcid and La Fleur, Linnea , et al. (2021) In Cancer Immunology, Immunotherapy 70(9). p.2577-2587
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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Check-point inhibitors, Immunotherapy, Lung cancer, Microenvironment, PD-L1 amplification
in
Cancer Immunology, Immunotherapy
volume
70
issue
9
pages
2577 - 2587
publisher
Springer
external identifiers
  • scopus:85101022029
  • pmid:33576873
ISSN
0340-7004
DOI
10.1007/s00262-020-02825-z
language
English
LU publication?
yes
id
22b09d70-0a95-4d62-92d8-ad461d978f1d
date added to LUP
2021-03-04 10:48:55
date last changed
2024-06-27 09:27:39
@article{22b09d70-0a95-4d62-92d8-ad461d978f1d,
  abstract     = {{<p>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.</p>}},
  author       = {{Goldmann, Torsten and Marwitz, Sebastian and Nitschkowski, Dörte and Krupar, Rosemarie and Backman, Max and Elfving, Hedvig and Thurfjell, Viktoria and Lindberg, Amanda and Brunnström, Hans and La Fleur, Linnea and Mezheyeuski, Artur and Mattsson, Johanna Sofia Margareta and Botling, Johan and Micke, Patrick and Strell, Carina}},
  issn         = {{0340-7004}},
  keywords     = {{Check-point inhibitors; Immunotherapy; Lung cancer; Microenvironment; PD-L1 amplification}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{9}},
  pages        = {{2577--2587}},
  publisher    = {{Springer}},
  series       = {{Cancer Immunology, Immunotherapy}},
  title        = {{PD-L1 amplification is associated with an immune cell rich phenotype in squamous cell cancer of the lung}},
  url          = {{http://dx.doi.org/10.1007/s00262-020-02825-z}},
  doi          = {{10.1007/s00262-020-02825-z}},
  volume       = {{70}},
  year         = {{2021}},
}