2023 World Conference on Lung Cancer (Posters)-P2.12. Tumor Microenvironment Remodeling Contributes to the Resistance to EGFR-TKI in EGFR-mutated Non-small Cell Lung Cancer

P2.12. Tumor Microenvironment Remodeling Contributes to the Resistance to EGFR-TKI in EGFR-mutated Non-small Cell Lung Cancer - PDF(Abstract)

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This study examined the tumor microenvironment (TME) changes before and after tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. Using scRNA-seq technology, the researchers analyzed the interactions between cancer cells, immune cells, and stromal cells in 23 patients at baseline and 11 patients after TKI resistance. They found that TKI treatment led to TME remodeling, with enhanced metabolism of cancer cells, specifically glycolysis and oxidative phosphorylation. T cells showed a unique exhaustion state, and the immune microenvironment was suppressed due to exhaustion T cells and macrophages. There was increased interaction between these two cell types. Additionally, a new resistance-related subgroup, SLC40A1macrophage, was identified, which expressed immunosuppressive-related genes CD84 and TREM2, leading to an immunosuppressive microenvironment and promoting tumor progression and TKI resistance. <br /><br />The findings highlight the importance of the TME in TKI resistance and provide a basis for understanding the mechanism of drug resistance in the TME. The enhanced metabolism of cancer cells and immune suppression caused by exhaustion T cells and macrophages contribute to TKI resistance. The interaction between macrophages and T cells further promotes tumor progression and TKI resistance. This study suggests potential therapeutic targets for NSCLC patients after TKI resistance, focusing on the TME. Overall, the research sheds light on the role of TME remodeling in TKI resistance in EGFR-mutated NSCLC patients, providing valuable insights for future exploration and therapeutic interventions.

Asset Subtitle

Xinyu Song

Meta Tag

Speaker Xinyu Song

Topic Metastatic NSCLC: Targeted Therapy - Other

Keywords

tumor microenvironment

tyrosine kinase inhibitor resistance

non-small cell lung cancer

epidermal growth factor receptor mutation

scRNA-seq technology

glycolysis

oxidative phosphorylation

exhaustion T cells

macrophages

immunosuppressive microenvironment