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dc.contributor.authorThapa, Bibhusal-
dc.contributor.authorSalcedo, Adriana-
dc.contributor.authorLin, Xihui-
dc.contributor.authorWalkiewicz, Marzena-
dc.contributor.authorMurone, Carmel-
dc.contributor.authorAmeratunga, Malaka-
dc.contributor.authorAsadi, Khashayar-
dc.contributor.authorDeb, Siddhartha-
dc.contributor.authorBarnett, Stephen A-
dc.contributor.authorKnight, Simon-
dc.contributor.authorMitchell, Paul L R-
dc.contributor.authorWatkins, D Neil-
dc.contributor.authorBoutros, Paul C-
dc.contributor.authorJohn, Thomas-
dc.identifier.citationJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2017; 12(5): 850-859en
dc.description.abstractResults of recent clinical studies of immune checkpoint inhibitors in malignant pleural mesothelioma (MPM) have dampened initial enthusiasm. However, the immune environment and targets of these treatments such as programmed cell death protein 1 and its ligand programmed death ligand 1 (PD-L1) have not been well characterized in MPM. Using a large cohort of patients, we investigated PD-L1 expression, immune infiltrates, and genome-wide copy number status and correlated them to clinicopathological features. Tissue microarrays were constructed and stained with PD-L1(clone E1L3N [Cell Signaling Technology, Danvers, MA]), cluster of differentiation 4, cluster of differentiation 8, and forkhead box P3 antibodies. PD-L1 positivity was defined as at least 5% membranous staining regardless of intensity, and high PD-L1 positivity was defined as at least 50%. Genomic DNA from a representative subset of 113 patients was used for genome-wide copy number analysis. The percent genome alteration was computed as a proxy for genomic instability, and statistical analyses were used to relate copy number aberrations to other variables. Among 329 patients evaluated, PD-L1 positivity was detected in 130 of 311 (41.7%), but high PD-L1 positivity was seen in only 30 of 311 (9.6%). PD-L1 positivity correlated with nonepithelioid histological subtype and increased infiltration with cluster of differentiation 4-positive, cluster of differentiation 8-positive, and forkhead box P3-positive lymphocytes. High PD-L1-positive expression correlated with worse prognosis (hazard ratio = 2.37, 95% confidence interval: 1.57-3.56, p < 0.001) in univariate analysis but not in multivariate analysis. Higher percent genome alteration was associated with epithelioid histological subtype and poorer survival (hazard ratio = 1.59, 95% confidence interval: 1.01-2.5, p = 0.04) but not PD-L1 expression. PD-L1 expression was associated with nonepithelioid MPM, poor clinical outcome, and increased immunological infiltrates. Increased genomic instability did not correlate with PD-L1 expression but was associated with poorer survival.en
dc.subjectCopy number aberrationsen
dc.subjectTumor-infiltrating lymphocytesen
dc.titleThe Immune Microenvironment, Genome-wide Copy Number Aberrations, and Survival in Mesothelioma.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Canceren
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Parkville, Victoria, Australiaen
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationInformatics and Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Canadaen
dc.identifier.affiliationDepartment of Pathology, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Austin Health, Olivia-Newton John Cancer and Wellness Centre, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Thoracic Surgery, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationGarvan Institute of Medical Research, Darlinghurst, New South Wales, Australiaen
dc.identifier.affiliationDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, Canadaen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australiaen
dc.type.austinJournal Article-
dc.type.austinResearch Support, Non-U.S. Gov't-, Khashayar
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.grantfulltextnone- Newton-John Cancer Research Institute- Surgery- Newton-John Cancer Research Institute- Surgery- Oncology- Newton-John Cancer Wellness and Research Centre- Newton-John Cancer Research Institute- Oncology- Newton-John Cancer Wellness and Research Centre-
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