WCLC 2025 - Posters & ePosters-P3.13.25 Comprehensive Immune Microenvironment Profile of EGFR-Mutant Non-Small Cell Lung Cancer Transformation Towards Small Cell Lung Cancer

P3.13.25 Comprehensive Immune Microenvironment Profile of EGFR-Mutant Non-Small Cell Lung Cancer Transformation Towards Small Cell Lung Cancer

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This study investigates the immune microenvironment of small cell lung cancer (SCLC) transformed from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following resistance to EGFR tyrosine kinase inhibitors (TKIs). Neuroendocrine transformation to SCLC (T-SCLC) is a key resistance mechanism with limited treatment options. The research profiled nine patients with EGFR mutations who developed T-SCLC and were treated with PD-1 axis immune checkpoint inhibitors (ICIs). Using RNA transcriptome sequencing and multiplex immunohistochemistry, the tumor immune microenvironment was analyzed and compared with primary SCLC (P-SCLC) gene expression data.<br /><br />Results showed that T-SCLC exhibits a significantly suppressed, immunosuppressive microenvironment compared to the original EGFR-mutant NSCLC. Key findings include downregulation of immune regulatory pathways, reduced immune cell infiltration, and lower immune signature scores such as MHC, T cell-inflamed gene expression profile (GEP), and interferon-gamma (IFN-γ) response. Despite this suppression, the immune microenvironment in T-SCLC remains more favorable than in P-SCLC, where immune signatures and checkpoints like LAG3 and TIGIT are even more downregulated.<br /><br />Clinically, the median progression-free survival and overall survival for T-SCLC patients treated with ICIs were 5.1 and 11.7 months, respectively. Differences in survival were noted between EGFR mutation subtypes, with patients harboring the L858R mutation tending toward poorer outcomes compared to those with 19del mutations.<br /><br />In conclusion, the study highlights the uniquely suppressed yet relatively more immune-active microenvironment in T-SCLC compared to P-SCLC. Given the limited therapies after SCLC transformation, future research should focus on developing individualized treatments aimed at reversing the immunosuppressive tumor milieu in T-SCLC to improve patient outcomes.

Asset Subtitle

hui yu

Meta Tag

Speaker hui yu

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

small cell lung cancer

SCLC

EGFR-mutant non-small cell lung cancer

NSCLC

tyrosine kinase inhibitors

immune microenvironment

neuroendocrine transformation

immune checkpoint inhibitors

PD-1 axis

immunosuppression