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Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Aujla, Savreet | - |
dc.contributor.author | Aloe, Christian | - |
dc.contributor.author | Vannitamby, Amanda | - |
dc.contributor.author | Hendry, Shona | - |
dc.contributor.author | Rangamuwa, Kanishka | - |
dc.contributor.author | Wang, Hao | - |
dc.contributor.author | Vlahos, Ross | - |
dc.contributor.author | Selemidis, Stavros | - |
dc.contributor.author | Leong, Tracy L | - |
dc.contributor.author | Steinfort, Daniel | - |
dc.contributor.author | Bozinovski, Steven | - |
dc.date | 2022-02-04 | - |
dc.date.accessioned | 2022-06-22T06:51:26Z | - |
dc.date.available | 2022-06-22T06:51:26Z | - |
dc.date.issued | 2022-05 | - |
dc.identifier.citation | Journal of thoracic oncology 2022; 17(5): 675-687 | en |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/30069 | - |
dc.description.abstract | Programmed death-ligand 1 (PD-L1) copy number gains may be predictive of clinical response to immunotherapy in NSCLC. This study investigated PD-L1 copy number variations in tumor resection and bronchoscopy biopsies and its relationship with PD-L1 tumor cell staining and inflammatory gene expression. PD-L1 gene copy number and mRNA expression were evaluated by real-time polymerase chain reaction in surgically resected NSCLC tumor biopsies (n = 87) and control biopsies (n = 20). A second cohort (n = 15) of bronchoscopy-derived tumor biopsies was analyzed, including multiple biopsies from the same patient across different anatomical sites. PD-L1 mRNA levels strongly correlated with PD-L1 tumor staining (r = 0.55, p < 0.0001). Interferon-γ mRNA expression associated with PD-L1 immune cell staining, but not PD-L1 tumor cell staining. In contrast, PD-L1 copy number positively associated PD-L1 tumor staining, but not PD-L1 immune cell staining. PD-L1 copy number analysis detected loss (15 of 87 = 17%) and gain (5 of 87 = 7%) of copy number. Tumors with low PD-L1 copy number expressed significantly reduced levels of inflammatory (interferon-γ, interleukin [IL]-6, IL-1β, MMP-9) and immunosuppressive (IL-10, transforming growth factor β) mediators. Analysis of bronchoscopy-derived biopsies revealed low heterogeneity in copy number values across different anatomical sites, in contrast to more variable PD-L1 mRNA expression. Low PD-L1 copy number tumors display reduced PD-L1 expression, reduced PD-L1 tumor cell staining, and an immunologic cold tumor microenvironment. Because PD-L1 copy number values are highly stable across different tumor regions, its evaluation may represent a robust and complimentary biomarker for predicting response to immunotherapy, where low copy number may predict lack of response. | en |
dc.language.iso | eng | |
dc.subject | Biomarkers | en |
dc.subject | Copy number | en |
dc.subject | Immunotherapy | en |
dc.subject | NSCLC | en |
dc.subject | PD-L1 | en |
dc.title | Programmed Death-Ligand 1 Copy Number Loss in NSCLC Associates With Reduced Programmed Death-Ligand 1 Tumor Staining and a Cold Immunophenotype. | en |
dc.type | Journal Article | en_US |
dc.identifier.journaltitle | Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer | en |
dc.identifier.affiliation | Respiratory and Sleep Medicine | en |
dc.identifier.affiliation | Department of Respiratory Medicine & Sleep Medicine, Royal Melbourne Hospital, Melbourne, Australia | en |
dc.identifier.affiliation | Faculty of Medicine, University of Melbourne, Parkville, Australia | en |
dc.identifier.affiliation | School of Health & Biomedical Sciences, RMIT University, Bundoora, Australia | en |
dc.identifier.affiliation | Department of Anatomical Pathology, St Vincent's Hospital, Melbourne, Australia | en |
dc.identifier.affiliation | The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia | en |
dc.identifier.pubmeduri | https://pubmed.ncbi.nlm.nih.gov/35124252/ | en |
dc.identifier.doi | 10.1016/j.jtho.2022.01.013 | en |
dc.type.content | Text | en_US |
dc.identifier.orcid | 0000-0002-1950-1505 | en |
dc.identifier.pubmedid | 35124252 | |
local.name.researcher | Leong, Tracy L | |
item.languageiso639-1 | en | - |
item.openairetype | Journal Article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Respiratory and Sleep Medicine | - |
crisitem.author.dept | Institute for Breathing and Sleep | - |
Appears in Collections: | Journal articles |
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