AXL up-regulates PD-L1 inducing gefitinib resistance in EGFR mutated NSCLC

Abstract

Targeted therapy for lung cancer research has advanced quickly in recent years, particularly EGFR-TKIs in the grouping of EGFR-mutant lung cancer, however clinical treatment has encountered difficulties with acquired drug resistance. Due to their great specificity, few adverse reactions, and prolonged tumor control duration, immune checkpoint inhibitors PD-1 and PD-L1 antibodies have emerged as a new therapy approach for NSCLC with the advancement of tumor biology. AXL, a gene that codes for receptor tyrosine kinases, has been linked to the growth, treatment resistance, and immunological imbalance of cancer cells. Its protein has been found to be abnormally expressed in NSCLC cancer tissues. Our study shows a positive regulatory link between AXL and PD-L1 expression, and AXL can upregulate PD-L1 to facilitate the development of acquired drug resistance in EGFR-mutant lung cancer treated with gefitinib. We offer additional understandings for AXL to overcome the gefitinib resistance mechanism in NSCLC, while also providing ideas for addressing targeted therapy resistance.