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PD-1, PD-L1 Protein Expression in Non-Small Cell Lung Cancer and Their Relationship with Tumor-Infiltrating Lymphocytes

Yayi He, Leslie Rozeboom, Christopher J. Rivard, Kim Ellison, Rafał Dziadziuszko, Hui Yu, Caicun Zhou, Fred R. Hirsch

Department of Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China (mainland)

Med Sci Monit 2017; 23:1208-1216

DOI: 10.12659/MSM.899909

Available online:

Published: 2017-03-09

BACKGROUND: Immunotherapy targeting the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint has shown the good outcomes in non-small cell lung cancer (NSCLC). We investigated PD-1 and PD-L1 protein expression and their correlation with tumor-infiltrating lymphocytes (TILs), and association with survival in NSCLC.
MATERIAL AND METHODS: The expression of PD-1 (NAT105, Cell Marque) and PD-L1 (28-8, Dako) protein was assessed in 55 NSCLC cell lines by immunohistochemistry (IHC). PD-1 (NAT105, Cell Marque) and PD-L1 (22C3, Dako) protein expression was evaluated by IHC, and TIL percentage was scored, in 139 surgically resected specimens from patients with NSCLC.
RESULTS: PD-1 was not expressed on NSCLC cell lines. PD-L1 was expressed on 20 NSCLC cell lines (36.4%). A total of 60 patient samples (43.2%) were positive for PD-1 on the TILs, and 25 (18.0%) were positive for PD-L1 on tumor cells. High expression of PD-1 on tumor cells was significantly correlated with higher expression of PD-L1 (P=0.026) and a higher percentage of TILs (P<0.001). In the Cox regression model, the odds ratio for PD-1 was 2.828 (95% CI: 1.325–11.165; P=0.013) and 8.579 (95% CI: 4.148–22.676; P<0.001) when PD-L1 and TILs were positive. Patients whose tumor cells were PD-L1 negative had a tendency for longer relapse-free survival (RFS) than patients who were PD-L1 positive (1.85 years, 95% CI: 0.77–2.93 vs. 0.97 years, 95% CI: 0.71–1.23; P=0.054).
CONCLUSIONS: PD-1 was expressed on TILs in tumor tissues in NSCLC patients. PD-L1 was expressed on both TILs and tumor tissues. PD-1 expression was correlated with PD-L1 on tumor cells and TILs. Patients who were PD-L1 positive tended to experience progression after surgery.

Keywords: Carcinoma, Non-Small-Cell Lung, Immunity, Active, Tumor Escape