Characterization of PD-L1 protein expression and CD8+ tumor-infiltrating lymphocyte density, and their associations with clinical outcome in small-cell lung cancer

Background: This study aimed to characterize programmed death ligand-1 (PD-L1) expression and CD8(+) tumor-infiltrating lymphocytes (TILs) density, and their impact on survival in patients with surgically resected small-cell lung cancer (SCLC). Methods: Fifty-six patients with surgically resected SCLC were included. PD-L1 protein expression and CD8(+) TILs were tested by immunohistochemistry. A meta-analysis of 15 articles with 1,505 patients that investigated the prevalence and prognostic significance of PD-L1 expression in SCLC was conducted. Results: Twenty-two (39.3%) patients had positive PD-L1 protein expression and 42 (75.0%) had high CD8(+) TILs density. PD-L1 expression level was not associated with CD8(+) TILs density (P=0.528). No any association between clinicopathological features and PD-L1 expression level or CD8(+) TILs density was observed. Positive PD-L1 expression [hazard ratio (HR) =0.374, P=0.002] and high CD8(+) TILs density (HR =0.429, P=0.008) were independently associated with significantly longer overall survival (OS), which remain the statistical significance in multivariate analyses (P=0.007, P=0.002; respectively). Meta-analysis showed that the prevalence of positive PD-L1 expression was 0.35 [95% confidence interval (CI), 0.22-0.48] and positive PD-L1 expression was correlated with markedly longer OS (HR =0.61; 95% CI, 0.31-0.91) in patients with SCLC. Conclusions: The prevalence of PD-L1 expression in surgically resected SCLC is lower than that published for NSCLC. There was no association between PD-L1 expression or CD8(+) TILs density and clinicopathological parameters. PD-L1 expression and CD8(+) TILs density was independently correlated with better outcome in patients with SCLC.