Programmed cell death-1 (PD-1) -targeted immunotherapy has become a promising treatment paradigm for patients with advanced non-small cell lung cancer (NSCLC). Clinical responses to checkpoint inhibition therapy in NSCLC have been associated with programmed death-1 ligand 1 (PD-L1) expression. However, the association between the expression of PD-L1 and PD-L2 and the clinicopathological features and patient outcomes in NSCLC remain unclear. We retrospectively analyzed 364 patients (158 squamous cell carcinoma and 206 adenocarcinoma) who underwent complete resection between 2009 and 2012. Expression of PD-L1 and PD-L2 was determined by immunohistochemistry. Correlations between PD-L1/PD-L2 expression and the clinicopathological features and survival parameters were analyzed and prognostic factors were identified. PD-L1 expression was significantly associated with moderate/heavy smoking history and serum squamous cell carcinoma antigen (SCCA) levels. Multivariate analysis showed patients with high PD-L1 expression had significantly shorter disease free survival (DFS, HR 1.411, P = 0.025) and overall survival (OS, HR 1.659, P = 0.004) than those with low PD-L1 expression at a 50% cutoff value. No significant association was found between PD-L2 expression and patient postoperative survival. Further stratification analysis revealed that in patients with moderate/heavy smoking history, elevated serum SCCA level, and squamous cell carcinoma, PD-L1 expression was associated with significantly shorter DFS and OS. Therefore, PD-L1 expression was correlated with moderate/heavy smoking history and elevated serum SCCA level in NSCLC patients, and was an independently poor predictor of survival.
Keywords: PD-L1; PD-L2; non-small cell lung cancer; prognostic biomarker; squamous cell carcinoma antigen.