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MET Pathway Inhibition Increases Chemo-Immunotherapy Efficacy in Small Cell Lung Cancer

ABSTRACT: Chemotherapy in combination with immunotherapy offers limited benefit in advanced Small Cell Lung Cancer (SCLC). This study explores the potential of combining MET pathway inhibition with chemo-immunotherapy for treating advanced SCLC. MET pathway activation triggers epithelial-mesenchymal transition, fostering chemoresistance and potentially undermining the efficacy of immunotherapy. In a SCLC mouse model, MET inhibition added to chemo-immunotherapy (anti-PD-L1) reduced tumor growth and extended survival by reshaping the tumor microenvironment, decreasing suppressive myeloid cells, and promoting an effective immune response. Analysis of patient samples revealed that myeloid-enriched immune infiltrates during chemo-immunotherapy might contribute to treatment resistance. Notably, elevated serum hepatocyte growth factor (HGF) levels were associated with a mesenchymal and inflamed phenotype, indicating that this subgroup of patients could potentially benefit from MET inhibitor (METi)-based therapeutic strategies.

ORGANISM(S): Mus musculus

PROVIDER: GSE262975 | GEO | 2025/06/20

REPOSITORIES: GEO

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