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dc.contributor.authorAmeratunga, M
dc.contributor.authorAsadi, K
dc.contributor.authorLin, X
dc.contributor.authorWalkiewicz, M
dc.contributor.authorMurone, C
dc.contributor.authorKnight, S
dc.contributor.authorMitchell, P
dc.contributor.authorBoutros, P
dc.contributor.authorJohn, T
dc.date.accessioned2021-02-12T00:20:11Z
dc.date.available2021-02-12T00:20:11Z
dc.date.issued2016-04-22
dc.identifierpii: PONE-D-15-51333
dc.identifier.citationAmeratunga, M., Asadi, K., Lin, X., Walkiewicz, M., Murone, C., Knight, S., Mitchell, P., Boutros, P. & John, T. (2016). PD-L1 and Tumor Infiltrating Lymphocytes as Prognostic Markers in Resected NSCLC. PLOS ONE, 11 (4), https://doi.org/10.1371/journal.pone.0153954.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/260548
dc.description.abstractINTRODUCTION: Immune checkpoint inhibition has shifted treatment paradigms in non-small cell lung cancer (NSCLC). Conflicting results have been reported regarding the immune infiltrate and programmed death-ligand 1 (PD-L1) as a prognostic marker. We correlated the immune infiltrate and PD-L1 expression with clinicopathologic characteristics in a cohort of resected NSCLC. METHODS: A tissue microarray was constructed using triplicate cores from consecutive resected NSCLC. Immunohistochemistry was performed for CD8, FOXP3 and PD-L1. Strong PD-L1 expression was predefined as greater than 50% tumor cell positivity. Matched nodal samples were assessed for concordance of PD-L1 expression. RESULTS: Of 522 patients, 346 were node-negative (N0), 72 N1 and 109 N2; 265 were adenocarcinomas (AC), 182 squamous cell cancers (SCC) and 75 other. Strong PD-L1 expression was found in 24% cases. In the overall cohort, PD-L1 expression was not associated with survival. In patients with N2 disease, strong PD-L1 expression was associated with significantly improved disease-free (DFS) and overall survival (OS) in multivariate analysis (HR 0.49, 95%CI 0.36-0.94, p = 0.031; HR 0.46, 95%CI 0.26-0.80, p = 0.006). In this resected cohort only 5% harboured EGFR mutations, whereas 19% harboured KRAS and 23% other. KRAS mutated tumors were more likely to highly express PD-L1 compared to EGFR (22% vs 3%). A stromal CD8 infiltrate was associated with significantly improved DFS in SCC (HR 0.70, 95%CI 0.50-0.97, p = 0.034), but not AC, whereas FOXP3 was not prognostic. Matched nodal specimens (N = 53) were highly concordant for PD-L1 expression (89%). CONCLUSION: PD-L1 expression was not prognostic in the overall cohort. PD-L1 expression in primary tumor and matched nodal specimens were highly concordant. The observed survival benefit in N2 disease requires confirmation.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titlePD-L1 and Tumor Infiltrating Lymphocytes as Prognostic Markers in Resected NSCLC
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0153954
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.departmentClinical School (Austin Health)
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS One
melbourne.source.volume11
melbourne.source.issue4
dc.rights.licenseCC BY
melbourne.elementsid1064408
melbourne.contributor.authorAMERATUNGA, MALAKA
melbourne.contributor.authorMitchell, Paul
melbourne.contributor.authorJohn, Thomas
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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