Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/30069
Full metadata record
DC FieldValueLanguage
dc.contributor.authorAujla, Savreet-
dc.contributor.authorAloe, Christian-
dc.contributor.authorVannitamby, Amanda-
dc.contributor.authorHendry, Shona-
dc.contributor.authorRangamuwa, Kanishka-
dc.contributor.authorWang, Hao-
dc.contributor.authorVlahos, Ross-
dc.contributor.authorSelemidis, Stavros-
dc.contributor.authorLeong, Tracy L-
dc.contributor.authorSteinfort, Daniel-
dc.contributor.authorBozinovski, Steven-
dc.date2022-02-04-
dc.date.accessioned2022-06-22T06:51:26Z-
dc.date.available2022-06-22T06:51:26Z-
dc.date.issued2022-05-
dc.identifier.citationJournal of thoracic oncology 2022; 17(5): 675-687en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/30069-
dc.description.abstractProgrammed 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.isoeng
dc.subjectBiomarkersen
dc.subjectCopy numberen
dc.subjectImmunotherapyen
dc.subjectNSCLCen
dc.subjectPD-L1en
dc.titleProgrammed Death-Ligand 1 Copy Number Loss in NSCLC Associates With Reduced Programmed Death-Ligand 1 Tumor Staining and a Cold Immunophenotype.en
dc.typeJournal Articleen_US
dc.identifier.journaltitleJournal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Canceren
dc.identifier.affiliationRespiratory and Sleep Medicineen
dc.identifier.affiliationDepartment of Respiratory Medicine & Sleep Medicine, Royal Melbourne Hospital, Melbourne, Australiaen
dc.identifier.affiliationFaculty of Medicine, University of Melbourne, Parkville, Australiaen
dc.identifier.affiliationSchool of Health & Biomedical Sciences, RMIT University, Bundoora, Australiaen
dc.identifier.affiliationDepartment of Anatomical Pathology, St Vincent's Hospital, Melbourne, Australiaen
dc.identifier.affiliationThe Walter and Eliza Hall Institute of Medical Research, Parkville, Australiaen
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/35124252/en
dc.identifier.doi10.1016/j.jtho.2022.01.013en
dc.type.contentTexten_US
dc.identifier.orcid0000-0002-1950-1505en
dc.identifier.pubmedid35124252
local.name.researcherLeong, Tracy L
item.languageiso639-1en-
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.cerifentitytypePublications-
crisitem.author.deptRespiratory and Sleep Medicine-
crisitem.author.deptInstitute for Breathing and Sleep-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

28
checked on Nov 8, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.