P35.20 Genomic Profiling and PD-L1 Expression Association Analysis in Epstein-Barr Virus (EBV)-infected Lung Cancer Patients

ABSTRACT

Introduction: COVID-19, a disease caused by coronavirus SARS-CoV-2, has drawn public attention worldwide. The virus is also associated with carcinogenesis. Epstein-Barr virus (EBV) was reported to be related to pulmonary lymphoepithelioma-like carcinoma (PLELC), a rare subtype of non-small cell lung cancer (NSCLC). However, the understanding of the treatment for EBV-infected NSCLC was still elusive. Immunotherapy that targets PD-1/PD-L1 has been utilized as a novel clinical treatment in recent years. Here, we focus on the genomic landscapes of lung cancers with EBV-infection and its correlation with PD-L1. Methods: Patients with both PD-L1 expression detection and genomic information were screened in HapLab database. HaploX 605-gene panel sequencing, covering 1.31 MB genome, was performed to analyze the genomic data of patients. PD-L1 expression was detected by immunochemistry. Bioinformatic analysis of genomic mutations and the correlation with the expression of PD-L1 were studied. Results: We analyzed the genomic profiles of 23 EBV-infected NSCLC patients. 11 cases of lung squamous-cell carcinoma (LUSC), 4 cases of lung adenocarcinoma (LUAD), 5 cases of lung pulmonary lymphoepithelioma-like carcinoma (PLELC), and 3 unidentified cases were included in this study. Collectively, 93 genome mutations of 67 genes were detected in 23 EBV-infection cases. Top 3 frequently mutated genes were TP53 (27%), CSMD3 (18%) and KMT2D (18%). The EBV-infected patients exhibited a low level of tumor mutation burden (TMB). The median TMB was 1.53 Muts/MB (ranging from 0 to 14.5 Muts/MB). Only 3 of 23 patients (13.0%) harbored the canonical driver mutations in NSCLC. Interestingly, 10/23 patients (43.5%) showed high expression of PD-L1, while 13/23 patients (56.5%) showed low expression. We also assessed the expression of PD-L1 in lung cancers with no EBV-infection (867 cases). Only 118/867 (13.6%) patients without EBV-infection presented high PD-L1 expression, while 749/867 (86.4%) presented low PD-L1 expression. Conclusion: EBV-infection can occur in different kinds of NSCLC, including LUSC, LUAD, and PLELC. TMB and driver mutations of EBV-infected NSCLC were not frequently observed as normal lung cancers, implying a different mechanism leading to EBV-infected lung cancers. Interestingly, EBV-infected NSCLC tended to have a high correlation with the expression of PD-L1. This may give a hint on the application of checkpoint blockade immunotherapy on EBV-infected NSCLC. [Formula presented] Keywords Epstein-Barr virus (EBV), PD-L1 expression, non-small cell lung cancer (NSCLC)