PD-L1 and Tumor Infiltrating Lymphocytes as Prognostic Markers in Resected NSCLC
AuthorAmeratunga, M; Asadi, K; Lin, X; Walkiewicz, M; Murone, C; Knight, S; Mitchell, P; Boutros, P; John, T
Source TitlePLoS One
PublisherPUBLIC LIBRARY SCIENCE
AffiliationClinical School (Austin Health)
Medicine and Radiology
Document TypeJournal Article
CitationsAmeratunga, 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.
Access StatusOpen Access
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.
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