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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 |
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