A single-nucleus transcriptomic characterization of EGFR G719X/S768I double-mutant lung adenocarcinoma identifies an immunosuppressive niche defined by COL4A3-CD44 interaction
Randomized trial identifies an immunosuppressive niche in EGFR double-mutant lung adenocarcinoma, suggesting new therapeutic targets.
Key Points
The study aims to characterize the tumor microenvironment of EGFR double-mutant lung adenocarcinoma and explore its therapeutic resistance mechanisms.
Single-nucleus RNA sequencing performed on tissues from EGFR double-mutant and non-mutant lung adenocarcinoma patients.
Integration of FFPE data with fresh-tissue scRNA-seq data from multiple cohorts to create an extensive cellular atlas.
Use of multiplex immunohistochemistry and pharmacogenomic profiling to validate findings and analyze drug sensitivity.
Identified an EMT-like malignant subpopulation uniquely enriched in EGFR double mutants with a lipid-glycosylation profile (event rate not provided).
Observed enhanced COL4A3-CD44 interactions with immunosuppressive alveolar macrophages in EGFR double mutants compared to non-mutants (event rate not provided).
Drug sensitivity analysis highlighted specific vulnerabilities in the EGFR double-mutant subtype (effect size not specified).