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

Abstract

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.

Neuroendocrine subtypes of small cell lung cancer differ in terms of immune microenvironment and checkpoint molecule distribution

“…6), whereas PD-1 and PD-L1 protein expression was not detectable in situ in any of the samples. This finding is similar to other researchers' that reported a relatively low rate of PD-L1 expression in SCLC up to 35.0% (with a very low cutoff point of 5% for PD-L1 positive/negative expression), which was consistently lower than that in NSCLC [59]. This difference can be explained by a variety of factors, including tumor stage and assays used.…”

Galectin-9-based immune risk score model helps to predict relapse in stage I–III small cell lung cancer

“…In SCLC, higher expression of CD3 was supposed to be correlated with better survival, whereas PD-L1 overexpression had no or even opposing effect on survival. 61 62 Conversely, Sun et al 63 explored that patients with SCLC who expressed higher PD-L1 and CD8 protein had longer OS. The level of FOXP3 has shown its statistically prognostic value in SCLC, especially among patients without metastasis.…”

FOXP3-based immune risk model for recurrence prediction in small-cell lung cancer at stages I–III

“… 46 47 Conversely, patients with SCLC with higher expression of PD-L1 and CD8 were found associated with better survival in the study of Sun et al . 48 Additionally, Bonanno and colleagues found that FOXP3 expression had prognostic value for OS in non-metastatic SCLC. 49 FOXP3 + /CD8 + T cell ratio was supposed as a negative prediction for patients’ prognosis in many cancers.…”