Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung cancer: a multicenter, retrospective analysis

Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell lung cancer (NSCLC) has improved the survival of patients. However, a significant percentage of patients do not respond. We examined the use of DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in stage IV NSCLC patients. We first established an epigenomic profile based on a microarray DNA methylation signature (EPIMMUNE) in a discovery set of 34 NSCLC tumor samples treated with nivolumab or pembrolizumab. The EPIMMUNE signature was validated in an independent set of 47 NSCLC cases. A derived DNA methylation marker was validated by a single-methylation assay in a validation cohort of 61 NSCLC patients.