Identification of clonal neoantigens derived from driver mutations in an EGFR mutated lung cancer patient benefitting from anti-PD-1

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been recommended as the first-line therapy for non-small cell lung cancer (NSCLC) patients harboringEGFRmutations. However, acquired resistance to EGFR-TKIs is inevitable. Although immune checkpoint blockades (ICBs) targeting the programmed cell death 1 (PD-1)/PD-ligand (L)1 axis have achieved clinical success for many cancer types, the clinical efficacy of anti-PD-1/PD-L1 blockades inEGFRmutated NSCLC patients has been demonstrated to be lower than those withoutEGFRmutations. Here, we reported an advanced NSCLC patient withEGFRdriver mutations benefitting from anti-PD-1 blockade therapy after acquiring resistance to EGFR-TKI. We characterized the mutational landscape of the patient with next-generation sequencing (NGS) and successfully identified specific T-cell responses to clonal neoantigens encoded byEGFRexon 19 deletion,TP53 A116TandDENND6B R398Qmutations. Our findings support the potential application of immune checkpoint blockades in NSCLC patients with acquired resistance to EGFR-TKIs in the context of specific clonal neoantigens with high immunogenicity. Personalized immunomodulatory therapy targeting these neoantigens should be explored for better clinical outcomes inEGFRmutated NSCLC patients.