Correlation between mutation burden of tumor and immunological/clinical parameters in considering biomarkers of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC)

Abstract

e23184 Background: There has been reported that mutation burden of solid tumor might probably be a predictive biomarker of efficacy of immune check point inhibitors, and the number of researches are still ongoing. Although the correlation of mutation burden between by whole exome sequence and by large targeted panel sequence has also been reported, neither method can be said to have solved technical and economical difficulty of using in clinical practice. Here we describe more convenient factors that can be used instead of mutation burden. Methods: 92 NSCLC patients with surgery during 2013-2015 in our institution were subjected for this study. Mutation burden in tumor samples was analyzed by whole exome sequence using Next Generation Sequencer. The major gene alteration was also analyzed by small targeted panel sequence. As immunological parameters, tumor infiltrating lymphocyte and PD-L1 expression in tumor were assessed by immunohistochemistry test using anti-CD8 antibody and anti-PD-L1 antibody. Statistical analysis was performed on mutation burden and the result of major gene alternation, immunohistochemistry, and clinical parameters. Results: There were 64 adenocarcinomas and 28 squamous cell carcinomas. The median value of mutation burden was 60 genes (10-502). The factors including squamous cell carcinoma, male, smoking history, EGFR-mutation negative, and TP53 alteration positive indicated close connection with higher mutation burden (p < 0.001) There were no significant difference in PD-L1 expression of tumor and tumor infiltrating lymphocyte. Multiple regression analysis showed that negative EGFR-mutation and positive TP53 alteration contribute to higher mutation burden (p < 0.05). Conclusions: Mutation burden in NSCLC tumor could be associated with EGFR-mutation and TP53 alteration status. These findings suggest that some major gene alteration make it possible to predict mutation burden, and could potentially be more simple predictive biomarkers of immune check point inhibitors.