PD-L1 Expression, Tumor-infiltrating Lymphocytes, and Clinical Outcome in Patients With Surgically Resected Esophageal Cancer

Objectives: To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer. Summary Background Data: PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required. Methods: Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis. The Cox proportional hazard model was used to compute the hazard ratio (HR) for mortality. Results: Compared with PD-L1 negative cases (n=252), PD-L1 positive cases (n = 53) showed significantly worse overall survival [log-rank P = 0.016; HR: 1.71; 95% confidence interval: 1.08–2.61; P = 0.024; multivariate HR: 1.69; 95% confidence interval: 1.05–2.67; P = 0.033]. TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001) and high CD8 expression ( P < 0.0001). A stratification based on PD-L1 expression and TIL status was also significantly associated with overall survival (log rank P < 0.0001). Conclusions: PD-L1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. In addition, the combination with TIL status enabled further classification patients according to clinical outcome. PD-L1 expression and TIL status may serve as predictive tissue biomarkers and can be used for patient selection in clinical trials of drugs targeting the PD-1/PD-L1 pathways.