P2.02-031 Relationship between PD-L1 Expression and EGFR/HER2 Signaling in Non-Small-Cell Lung Cancer

Abstract

Immunocheckpoint inhibitors targeting PD-1/PD-L1 axis have shown promising results in patients with non-small-cell lung cancer (NSCLC). It is well known that PD-L1 is induced by IFNg, however recent study shows that EGFR also affects PD-L1 expression in tumor cells. We evaluated the expressions of PD-L1, EGFR, and HER2 in tumor tissues collected from patients with pStage IA–IIIA NSCLC using immunohistochemistry. Intensity scoring for staining was calculated with H-score (0-300). The relationships between their expression and clinicopathological characteristics were evaluated. For in vitro assay, the expression of PD-L1 was evaluated by flow cytometric analysis while cell signaling pathways were assessed with Phospho-Receptor Tyrosine Kinase (RTK) array in LC2/ad human lung adenocarcinoma cell line. Of the total 91 tumors, 13 cases (14%) showed PD-L1 overexpression, 12 cases (13%) showed EGFR overexpression, and 35 cases (38%) showed HER2 overexpression in tumor cells. PD-L1 overexpression associated with poor clinical outcome and was positively correlated with EGFR expression while inversely correlated with HER2. To assess the regulation mechanism of PD-L1 expression via EGFR/HER2 signaling, LC2/ad cells were treated with EGF with or without inhibition of EGFR or HER2, after which PD-L1 expression was evaluated using flow cytometry. Consistent with previous reports, PD-L1 expression was clearly enhanced by EGF, and either EGFR-tyrosine kinase inhibitor Gefitinib and siRNA for EGFR blocked EGF-induced PD-L1 overexpression in LC2/ad cells. On the other hand, we found that siRNA for HER2 could not block EGF-induced PD-L1 overexpression. We compared EGF-induced signaling with IFNg-induced one by RTK array, and found EGF stimulation activated AKT, MAPK, and S6 ribosomal protein while IFN-g activated STAT1. PD-L1 overexpression is associated with poor prognosis and is positively correlated with EGFR expression but inversely correlated with HER2 expression in NSCLC. The expression mechanism of PD-L1 is different between EGFR and HER2 signaling in LC2/ad cell line. Additionally, both EGF and IFNg enhance PD-L1 expression but via different pathway in NSCLC cell line LC2/ad.