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(Slides)

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This study explored the role of the tumor microenvironment (TME) in the development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC) patients with EGFR mutations. Using single-cell RNA sequencing technology, the researchers analyzed the changes in the TME before and after TKI resistance in patients with EGFR-mutated NSCLC. They found that TKI treatment led to remodeling of the TME, with increased interactions between cancer cells and immune cells. After TKI resistance, the metabolism of cancer cells was enhanced, specifically glycolysis and oxidative phosphorylation. T cells showed a state of exhaustion, and the immune microenvironment was suppressed by exhaustion T cells and macrophages. The interaction between these two types of cells was increased. The study also identified a new resistance-related subgroup called SLC40A1 macrophage, which expressed immunosuppressive genes. Further experiments confirmed that this subgroup did not affect the resistance of cancer cells themselves but promoted an immunosuppressive microenvironment and tumor progression. Overall, the findings suggest that after TKI resistance in EGFR-mutated NSCLC patients, the TME plays a crucial role in promoting drug resistance. This study provides insights into the mechanism of drug resistance in the TME and paves the way for the development of potential therapeutic targets.

Asset Subtitle

Xinyu Song

Meta Tag

Speaker Xinyu Song

Topic Metastatic NSCLC: Targeted Therapy - Other

Keywords

tumor microenvironment

EGFR-TKIs

non-small cell lung cancer

EGFR mutations

single-cell RNA sequencing

TKI resistance

glycolysis

oxidative phosphorylation

exhaustion T cells

macrophages