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Title: PD-L1 and tumor infiltrating lymphocytes as prognostic markers in resected NSCLC
Austin Authors: Ameratunga, Malaka;Asadi, Khashayar ;Lin, Xihui;Walkiewicz, Marzena;Murone, Carmel ;Knight, Simon;Mitchell, Paul L R ;Boutros, Paul;John, Thomas 
Affiliation: Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia
Department of Pathology, Austin Health, Heidelberg, Victoria, Australia
Informatics & Biocomputing Program, Ontario Institute for Cancer Research, Toronto, Canada
The Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Thoracics, Austin Health, Heidelberg, Victoria, Australia
Department of Medical Biophysics, University of Toronto, Toronto, Canada
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada
School of Cancer Medicine, La Trobe University, Victoria, Australia
University of Melbourne, Melbourne, Victoria, Australia
Issue Date: 22-Apr-2017
Date: 2017-04-22
Publication information: PLoS One 2017: 11(4): e0153954
Abstract: INTRODUCTION: 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.
DOI: 10.1371/journal.pone.0153954
Journal: PLoS One
PubMed URL:
Type: Journal Article
Subjects: Lung neoplasms
Lymphocytes, tumor-infiltrating
Biomarkers, tumor
Antigens, CD274
Appears in Collections:Journal articles

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