ArticleJournal of cellular and molecular medicine2025
The Critical Role of APOE+ Macrophages in the Immune Microenvironment and Prognosis of Lung Adenocarcinoma.
Article in Journal of cellular and molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- CTSB-positive tumor-associated macrophages shape prognosis and therapeutic response in lung adenocarcinoma.Translational oncology · 2026Article
- Macrophage spatiotemporal plasticity in pulmonary diseases: decoding the niche at single-cell resolution.Frontiers in immunology · 2026Review
- The Critical Role of APOE+ Macrophages in the Immune Microenvironment and Prognosis of Lung Adenocarcinoma.Journal of cellular and molecular medicine · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
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Abstract
The immunoregulatory functions and clinical implications of APOE+ macrophages within the tumour microenvironment of lung adenocarcinoma remain incompletely defined. In this study, single-cell transcriptome analysis revealed distinct subsets of APOE+ macrophages, and subsequent CellChat analyses highlighted that these cells predominantly interact with other components of the tumour microenvironment via MIF-(CD74+CXCR4) and MIF-(CD74+CD44) signalling pathways, thereby contributing to the establishment of an immunosuppressive milieu. Integrating mutation profiles with multiple machine learning techniques, we developed an APOE+ Macrophage-related Risk Model (ARM) through a combination of RSF and Ridge approaches, achieving the highest prognostic accuracy (C-index) among all tested algorithms. The robustness and predictive value of the ARM model were validated across seven public cohorts and three prospective immunotherapy cohorts. Patients classified in the low-ARM group consistently exhibited better prognoses, as demonstrated by survival analyses, ROC curves and PCA discrimination. Additionally, multiplex immunofluorescence analysis in the in-house cohort confirmed significantly decreased infiltration of CD4+, CD8+ and CD20+ immune cells in the high-ARM group, further supporting a more pronounced immunosuppressive microenvironment in these patients. Collectively, our findings not only clarify the critical role of APOE+ macrophages in shaping the immune landscape and prognosis of lung adenocarcinoma, but also provide a validated, practical risk model for individualised patient prognostication and clinical management.
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