Association of PD-1, PD-L1, and CTLA-4 Gene Expression and Clinicopathologic Characteristics in Patients With Non-Small-Cell Lung Cancer

Clinicopathologic characteristics of patients with nonesmall-cell lung cancer (NSCLC) related to positive responses to immunotherapy are currently unknown. In our study, we found that alterations in programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 expression at the mRNA level in lung tumoral tissue are not related to age, sex, smoking status, histological type, pathological stage, or tumor differentiation degree. However, PD-1 and PD-L1 overexpression might predict worse survival in stage I NSCLC patients and in well differentiated tumors. Introduction: Recent studies show a potential benefit of therapies that target programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitory checkpoints in a subgroup of patients with nonesmall-cell lung cancer (NSCLC), without the clinicopathologic characteristics related to positive responses to these treatments being well determined. The aim of this study was to determine PD-1, PD-L1, and CTLA-4 gene expression at the mRNA level in tumoral tissue from patients with NSCLC and analyze their possible relationship with the clinicopathological characteristics and their potential prognostic role. Patients and Methods: PD-1, PD-L1, and CTLA-4 expression levels were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction in fresh-frozen tumor and normal adjacent lung tissue samples from 78 patients with NSCLC. Later, a significant association between mRNA levels, clinicopathologic characteristics, and patient's survival was assessed. Results: No significant correlation between gene expression levels and sex, age, histological type, smoking status, pathologic stage, or tumor differentiation was found. However, higher levels of PD-1 were significantly associated with worse prognosis in patients with NSCLC, and PD-L1 overexpression was associated with a worse prognosis in stage I patients and in Grade 1 to 2 tumors. Conclusion: Alterations in PD-1/PD-L1 and CTLA-4 expression in lung tumoral tissue seem not to be related to age, sex, smoking status, histological type, pathological stage, or tumor differentiation degree. However, PD-1 and PD-L1 overexpression might predict worse survival in patients with stage I NSCLC and in well differentiated tumors. (C) 2016 Elsevier Inc. All rights reserved.