Programmed Death-Ligand 1 Expression Predicts Tyrosine Kinase Inhibitor Response and Better Prognosis in a Cohort of Patients With Epidermal Growth Factor Receptor Mutation-Positive Lung Adenocarcinoma

The oncogenic driver epidermal growth factor receptor (EGFR) mutations upregulate immune checkpoint proteins programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) in in vitro and in vivo models of nonesmall-cell lung cancer (NSCLC). Immunohistochemistry revealed that PD-L1 and PD-1 were positive in 53.6% and 32.1% of tumor specimens in a cohort of 56 patients with NSCLC carrying EGFR mutations, respectively. PD-L1 expression correlated with a better response to EGFR tyrosine kinase inhibitors and longer survival. Background: The immune checkpoint proteins programmed death-1/ligand (PD-1/PD-L1) play a critical role in immune escape of tumor cells. In models of epidermal growth factor receptor (EGFR)-driven nonesmall-cell lung cancer (NSCLC), EGFR signal upregulates PD-1/PD-L1. However, data on the clinical significance of PD1/PD-L1 expression in patients with the subtype of NSCLC carrying EGFR mutations remain limited. Materials and Methods: Immunohistochemistry was performed to evaluate the expression of PD-1, PD-L1, and CD4+ and CD8+ tumor-infiltrating T lymphocytes (TILs). Results: In a cohort of 56 patients, PD-L1 and PD-1 was positive in 53.6% and 32.1% of tumor specimens, respectively. PD-L1+ patients had a significantly greater disease-control rate (P = .004), in association with longer progression-free survival (P = .001) after EGFR-tyrosine kinase inhibitor (TKI) therapy and overall survival (P = .004), and no correlation between PD-1 positivity and clinical outcomes was observed. PD-L1 expression was not significantly associated with either clinicopathologic features or TILs. Conclusions: These findings suggest that this subtype of EGFR mutation-positive NSCLC is highly eligible for PD-1/PD-L1 immunotherapy. PD-L1 might represent a favorable biomarker candidate for the response to EGFR-TKIs and outcomes of these patients with NSCLC. (C) 2015 Elsevier Inc. All rights reserved.