Machine learning identifies TIME subtypes linking EGFR mutations and immune states in lung adenocarcinoma.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41299024.
- Also identified by DOI 10.1038/s41746-025-02172-2 and PMC identifier 12749019.
- Licence recorded as CC BY-NC-ND.
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Abstract
Epidermal growth factor receptor (EGFR) mutation is a key oncogenic driver in lung adenocarcinoma (LUAD), but its impact on the tumor immune microenvironment (TIME) remains unclear. By integrating single-cell transcriptomes from 153 LUAD samples using machine learning, we generated an atlas of over one million cells that delineates immune heterogeneity. EGFR-mutant tumors exhibited enrichment of TIGIT<sup>+</sup>regulatory T cells, neutrophils, and macrophages, whereas wild-type tumors contained abundant ZNF683<sup>+</sup>CD8<sup>+</sup>tissue-resident memory T cells, diverse memory B cells, and FGFBP2<sup>+</sup>CD16<sup>high</sup> natural killer cells, reflecting an immune-active TIME. Non-negative matrix factorization defined five TIME subtypes, with EGFR-mutant patients clustering into immunosuppressive profiles linked to poor prognosis. Flow cytometry and mouse models confirmed the cytotoxic and PD-1 blockade-enhancing functions of FGFBP2<sup>+</sup>NK cells. These findings reveal distinct TIME landscapes in EGFR-mutant LUAD and illustrate the potential of machine learning-based immunogenomic analysis to inform precision immunotherapy.