title: PD-1, PD-L1 Protein Expression in Non-Small Cell Lung Cancer and Their Relationship with Tumor-Infiltrating Lymphocytes.
abstract: 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.
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China (mainland).|Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Yayi
authors.initials: Y
authors.lastname: He
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Rozeboom
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rivard
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Ellison
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Dziadziuszko
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China (mainland).
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor