WCLC 2025 - Posters & ePosters-P2.02.31 The Changes of Macrophage in EGFR Mutant TKI-Resistant Patients With Lung Cancer

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This study investigates macrophage changes in lung cancer patients with epidermal growth factor receptor (EGFR) mutations who develop resistance to tyrosine kinase inhibitors (TKIs). EGFR-mutated lung cancers show limited sensitivity to immune checkpoint inhibitors (ICIs), and options after TKI resistance are scarce. However, prior clinical trials (ORIENT31) by the authors demonstrated that ICI-based combination therapies improve progression-free survival in TKI-resistant patients, highlighting the need to understand the underlying immune mechanisms.<br /><br />Using single-cell RNA sequencing, tumor biopsies from three patient groups—EGFR wild-type (WT), EGFR-mutant (MUT), and TKI-resistant (EGFR-TKI)—were analyzed to characterize differences in immune microenvironments. Analysis focused on myeloid cells, especially macrophage subsets. The results revealed significant differences in macrophage composition among groups, with particular enrichment of SLC40A1-expressing macrophages in TKI-resistant tumors. Gene set enrichment analysis indicated that these SLC40A1 macrophages are involved in antigen presentation pathways, suggesting a role in modulating anti-tumor immunity.<br /><br />The study concludes that macrophages, especially the SLC40A1 subset, are central in shaping the immune microenvironment of TKI-resistant EGFR-mutant lung cancer. Importantly, SLC40A1 macrophages may serve as predictive biomarkers for immunotherapy response in these patients. These insights offer valuable guidance for future clinical applications of ICIs in TKI-resistant lung cancer, potentially improving outcomes by tailoring immunotherapy strategies based on tumor immune profiles.<br /><br />In summary, the research delineates macrophage-mediated immune changes associated with TKI resistance and supports targeting or monitoring macrophage subsets to optimize immunotherapeutic efficacy in EGFR-mutant lung cancer patients.

Asset Subtitle

Shuxin Zhu

Meta Tag

Speaker Shuxin Zhu

Topic Tumor Biology – Preclinical Biology

Keywords

EGFR mutations

lung cancer

tyrosine kinase inhibitors resistance

macrophage subsets

SLC40A1 macrophages

immune checkpoint inhibitors

single-cell RNA sequencing

tumor microenvironment

immunotherapy biomarkers

antigen presentation