Gene expression profiles of peripheral blood mononuclear cells from patients with advanced non-small cell lung cancer treated with anti-PD-1 monoclonal antibodies.

Abstract

e14107 Background: Anti-PD-1 monoclonal antibodies have improved the outcome for patients with advanced non-small cell lung cancer (NSCLC). The goal of this study is to characterize the longitudinal gene expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with advanced NSCLC treated with anti-PD-1 monoclonal antibodies and to evaluate the potential of this technology to predict response to therapy. Methods: PBMCs were collected using density centrifugation from patients with stage III/IV NSCLC before the first (T0) and second (T1) treatments, and, for responding patients, before the third (T2), fourth (T3), fifth (T4) and sixth (T5) treatments. Total RNA was extracted, and libraries were prepared using TruSeq Stranded mRNA LT Sample Prep Kit and sequenced by Illumina NextSeq. The paired-end reads were mapped to human reference hg38 using STAR and gene expressions were calculated using RSEM. Longitudinal differential gene expression with pathway analysis and principal component analysis (PCA) was performed across all time points. Genes with Bonferroni-adjusted p values < 0.05 were selected for pathway enrichment analysis with DAVID. Results: Nine of 15 patients have been enrolled. Six patients had a PR by RECIST 1.1, 2 patients have had stable/PD, 1 patient too early. Differential gene expression (DE) is available for the 8 patients with response assessment. There was differential expression of certain genes between T0 and T1 in the following pathways in responders but not in stable/PD: T cell receptor complex (p = 3.1E-6), regulation of immune response (p = 2.5E-5), T cell costimulation (p = 3.9E-3) were upregulated. CD24 is downregulated, while C4B is upregulated. Using PCA analysis we detected strong signal from the beta-hemoglobin HBB transcript. We observed HBG1 and HBM consistently upregulated at T1 (adjusted p = 7.9E-19 and p = 2.3E-10 respectively) through to T4 (adjusted p = 8.8E-27 and p = 3.8E-18 respectively). Conclusions: Anti-PD-1 monoclonal antibodies induce DE of genes in PBMCs from patients with advanced NSCLC. This technology may provide a predictive test for response to anti-PD-1 monoclonal antibodies.