Immunotherapy for patients with EGFR-TKI-resistant non-small-cell lung cancer: Potential mechanisms, efficacy predictors, and therapeutic integration

Immunotherapy has revolutionized the treatment landscape of advanced non-small-cell lung cancer (NSCLC). However, its efficacy in patients with epidermal growth factor receptor ( EGFR )-mutant NSCLC, particularly after failure of EGFR-tyrosine kinase inhibitors (TKIs), remains unclear and highly heterogeneous across individuals. This difference in treatment response is closely associated with the dynamic remodeling of the tumor microenvironment (TME) driven by the selective pressure of EGFR-TKIs. This review outlines the evolution of the TME during EGFR-TKI treatment and after the development of TKI resistance. Additionally, it summarizes current clinical evidence regarding immunotherapy after EGFR-TKI resistance, and discusses predictive biomarkers and novel therapeutic approaches. By integrating mechanistic insights with clinical translation, this review provides a comprehensive perspective on the immunotherapy landscape after TKI failure, aiming to identify patient subgroups most likely to benefit from immunotherapy and optimize treatment strategies for EGFR -mutant NSCLC.