Objective This study aims to investigate the immune landscape of the epidermal growth factor receptor exon 19 deletion (EGFR 19del) lung adenocarcinoma tumor microenvironment, focusing on the characteristics and roles of neutrophils to provide new strategies for immunotherapy.

Methods Single-cell data from EGFR 19del tumor tissues were analyzed for cellular heterogeneity, intercellular communication, ligand-receptor interactions, and functional enrichment analysis of neutrophil-related genes.

Results We found altered cell proportions in the EGFR 19del tumor environment, with neutrophils participating in inflammatory responses and cell chemotaxis through enhanced interactions of key ligand-receptor pairs such as OSM-(OSMR-LIF), C-X-C motif chemokine ligand 1(CXCL1), and chemokine (C–C motif) ligand 18(CCL18). Additionally, neutrophils play a key role in innate immunity, cytokine production, and pattern recognition receptor activity, and function in NOD-like receptor and chemokine signaling pathways.

Conclusion Neutrophils may play a crucial role in the development and therapeutic response of EGFR 19del lung adenocarcinoma by regulating inflammation and immune cell chemotaxis, affecting the tumor microenvironment and providing new targets for immunotherapy.