Immune checkpoint inhibitors in EGFR-mutated non-small cell lung cancer: Dusk or Dawn?

Abstract

Although immune checkpoint inhibitors (ICIs) that target programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) axis have significantly shifted the treatment paradigm in advanced non-small cell lung cancer (NSCLC), clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Several predictive biomarkers (e.g. PD-L1 expression, tumor mutation burden, etc.), which have been validated in EGFR-wild type NSCLC, however, are not efficacious in EGFR-mutated tumors, suggesting the unique characteristics of tumor microenvironment (TME) of EGFR-mutated NSCLC. Herein, we firstly summarized the clinical evidence on the efficacy of ICIs in patients with EGFR-mutated NSCLC. Then, the cancer immunogram features of EGFR-mutated NSCLC was depicted to visualize the state of cancer-immune system interactions, including tumor foreignness, tumor sensitivity to immune effectors, metabolism, general immune status, immune cell infiltration, cytokines and soluble molecules. We further discussed the potential subpopulations with EGFR mutations that could benefit from ICI treatment. Finally, we put forward future strategies to adequately maximize the efficacy of ICI treatment in patients with EGFR-mutated NSCLC in the upcoming era of combination immunotherapies.