Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/30069
Title: Programmed Death-Ligand 1 Copy Number Loss in NSCLC Associates With Reduced Programmed Death-Ligand 1 Tumor Staining and a Cold Immunophenotype.
Austin Authors: Aujla, Savreet;Aloe, Christian;Vannitamby, Amanda;Hendry, Shona;Rangamuwa, Kanishka;Wang, Hao;Vlahos, Ross;Selemidis, Stavros;Leong, Tracy L ;Steinfort, Daniel;Bozinovski, Steven
Affiliation: Respiratory and Sleep Medicine
Department of Respiratory Medicine & Sleep Medicine, Royal Melbourne Hospital, Melbourne, Australia
Faculty of Medicine, University of Melbourne, Parkville, Australia
School of Health & Biomedical Sciences, RMIT University, Bundoora, Australia
Department of Anatomical Pathology, St Vincent's Hospital, Melbourne, Australia
The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
Issue Date: May-2022
Date: 2022-02-04
Publication information: Journal of thoracic oncology 2022; 17(5): 675-687
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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/30069
DOI: 10.1016/j.jtho.2022.01.013
ORCID: 0000-0002-1950-1505
Journal: Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
PubMed URL: 35124252
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/35124252/
Type: Journal Article
Subjects: Biomarkers
Copy number
Immunotherapy
NSCLC
PD-L1
Appears in Collections:Journal articles

Show full item record

Page view(s)

34
checked on Dec 24, 2024

Google ScholarTM

Check


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