The Resistance Mechanism of ICI to EGFR and the Improvement Strategies

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide, among which non-small cell lung cancer (NSCLC) is the most common pathological subtype. Immune checkpoint inhibitors (ICIs) significantly improve the survival prognosis of patients with advanced lung cancer and enhance their quality of life by targeting molecules such as PD-1/PD-L1. However, the efficacy of ICI varies significantly. Due to the presence of EGFR mutant patients (over 50%) in the NSCLC population, these patients are insensitive to PD-L1 ICI immunosuppressive agents, resulting in limitations of PD-L1 ICI therapy. Therefore, it is necessary to systematically review the current application status, resistance mechanisms, and biomarker optimization strategies of ICI in EGFR mutant patients. This article summarizes the efficacy differences of ICI in different EGFR mutant subtypes, discusses the resistance mechanisms of ICI, and points out the optimization direction of ICI for the treatment of EGFR mutant-type lung cancer. Finally, it is found that although PD-L1 is highly expressed in EGFR mutant patients, they still have resistance; the factors of resistance include intrinsic factors and microenvironment factors; neoadjuvant immunotherapy (such as IMpower130) provides prospects for ICI treatment, but the biomarkers need to be further optimized. In conclusion, ICI has provided breakthrough progress in the treatment of EGFR-type lung cancer, but it still needs to solve the resistance problems and limitations in treatment. This article, through reviewing the above content, provides a reference for the precise decision-making and future research directions of EGFR mutant-type lung cancer treatment.