ArticleDiscover oncology2025
Dissecting macrophage heterogeneity and kaempferol in lung adenocarcinoma: a single-cell transcriptomic approach and network pharmacology.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Molecular Mechanisms of the Anticancer Activity of the Flavonoid Kaempferol: A Comprehensive Review.Journal of cancer prevention · 2026Review
- Single-cell sequencing and network pharmacology coupled with molecular docking and experimental validation reveal the effects of YPFS on macrophages in stage I non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Kaempferol as a multifaceted immunomodulator: implications for inflammation, autoimmunity, and cancer.Frontiers in immunology · 2025Review
- AI driven network pharmacology: Multi-scale mechanisms of traditional Chinese medicine from molecular to patient analysis.Computational and structural biotechnology journal · 2025Review
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5 authors.
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Abstract
backgroundLung adenocarcinoma (LUAD) is a leading form of non-small cell lung cancer characterized by a complex tumor microenvironment (TME) that influences disease progression and therapeutic response. Tumor-associated macrophages (TAMs) within the TME promote tumorigenesis and evasion of immune surveillance, though their heterogeneity poses challenges in understanding their roles and therapeutic targeting. Additionally, traditional Chinese medicine (TCM) offers potential anti-cancer agents that could modulate the immune landscape.
methodsWe conducted single-cell RNA sequencing (scRNA-seq) on LUAD samples, performing an in-depth analysis of macrophage populations and their expression signatures. Network pharmacology was used to identify TCM components with potential TAM-modulatory effects, focusing on Astragalus membranaceus. Pseudotime trajectory analysis, immunofluorescence staining, and in vitro assays examined the functional roles of TAMs and the effects of selected compounds on macrophage polarization.
resultsOur scRNA-seq analysis identified notable heterogeneity among macrophages, revealing predominant M2-like phenotypes within TAMs. Network pharmacology highlighted active TCM ingredients, including quercetin, isorhamnetin, and kaempferol, targeting genes related to macrophage function. Survival analysis implicated AHSA1, CYP1B1, SPP1, and STAT1 as prognostically significant factors. Further experiments demonstrated kaempferol's efficacy in inhibiting M2 polarization, underlining a selective influence on TAM functionality.
conclusionsThis study delineates the diverse macrophage landscape in LUAD and suggests a pivotal role for STAT1 in TAM-mediated immunosuppression. Kaempferol, identified from TCM, emerges as an influential agent capable of altering TAM polarization, potentially enhancing anti-tumoral immunity. These findings underscore the translational potential of integrating TCM-derived compounds into immunotherapeutic strategies for LUAD.
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