Distinct prognostic values of programmed death-ligand 1 and programmed cell death protein 1 in lung adenocarcinoma and squamous cell carcinoma patients.

Abstract

BackgroundAlthough immunotherapy has demonstrated similar clinical activities in the treatment of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC), several studies have shown programmed death-ligand 1 (PD-L1) to have different predictive roles in ADC and SCC. This study was conducted to compare the different functions of PD-L1/programmed cell death protein 1 (PD-1) pathway in these malignancies.MethodsA multi-dimensional analysis based on public databases and 2 independent cohorts including 262 patients with lung cancer was performed. Immunohistochemistry (IHC) and fluorescence-based multiplexed staining were used to detect the immune factors.ResultsPD-L1 was observed to have different expressions and regulatory mechanisms between SCC and ADC. PD-L1 was significantly increased from the messenger RNA (mRNA) to protein levels in the SCC group compared with the ADC group. Also, PD-L1 on tumor cells (TCs) was positively correlated with CD8+ tumor lymphocyte infiltrates in ADC, but not in SCC. More importantly, PD-L1 was considered to be an independent predictor of overall survival (OS) for ADC patients. In contrast, in SCC patients, PD-1+ tumor-infiltrating lymphocytes (TILs) were considered a poor prognostic predictor.ConclusionsThese findings showed that PD-L1 in ADC and PD-1+ TILs in SCC respectively indicates T-cell function, which plays a crucial role in determining prognosis. The distinct functions of the biomarkers between ADC and SCC might provide potential avenues for guiding anti-PD-1/PD-L1 immunotherapy.