ArticleCancer discovery2024
EGFR-driven lung adenocarcinomas coopt alveolar macrophage metabolism and function to support EGFR signaling and growth.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 29 citations in OpenAlex.
- Lipid Metabolic Reprogramming in Lung Cancer: Mechanisms and Therapeutic Targets in the Tumor Microenvironment.International journal of cancer · 2026Review
- Multifocal ground-glass opacities in lung cancer: a narrative review of genomic evolution, immune ecology, and biology-informed clinical management.Journal of thoracic disease · 2026Review
- Cancer heterogeneity explored through immune cell deconvolution of the tumor microenvironment.Quantitative biology (Beijing, China) · 2026Article
- Lipid metabolic reprogramming of tumor-associated macrophages drives resistance to immune checkpoint blockade in lung cancer: a narrative review of mechanisms and therapeutic strategies.Translational lung cancer research · 2026Review
- CircSMAD4 shapes matrix-remodeling TAMs in lung adenocarcinoma.Non-coding RNA research · 2026Article
- AMPK Suppresses Multiple Forms of Cell Death Including Disulfidptosis in Tumor-Associated Macrophages During Tumor Progression.International journal of molecular sciences · 2026Article
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Atlas-Guided Nanocarrier Strategies Targeting Spatial NTRK2/MAPK Signaling in EGFR-TKI-Resistant Niches of Esophageal Squamous Cell Carcinoma.Pharmaceutics · 2026Review
- Lipids regulate epidermal growth factor receptor activation by its ligands.Biochemical Society transactions · 2026Review
- Targeting lung cancer: synergistic therapeutic strategy of cuproptosis and immunogenic cell death.Frontiers in cell and developmental biology · 2026Review
- Roles of Cellular Neighborhoods in Lung Cancer.Journal of Cancer · 2026Review
- A novel mouse cell line model reveals the tumor intrinsic and immune characteristics of EGFR-mutant lung cancer.Theranostics · 2026Article
- Effect of Nano-Gefitinib on Solid Ehrlich Carcinoma via Targeting EGFR, RIPK2 Pathways, and Macrophage Reprogramming.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Positive and negative roles of myeloid cells in cancer immunotherapy.Journal for immunotherapy of cancer · 2025Review
- Graph-based deep learning for integrating single-cell and bulk transcriptomic data to identify clinical cancer subtypes.Briefings in bioinformatics · 2025Article
- SLC34A2 inhibits tumorigenesis and progression via upregulating LRRK2/TTF-1/SELENBP1 axis in lung adenocarcinoma.Cancer gene therapy · 2025Article
- Orthotopically Implanted Murine Lung Adenocarcinoma Cell Lines for Preclinical Investigations.Cancers · 2025Review
- The Emerging Roles of Metabolic Reprogramming in Non-Small Cell Lung Cancer Progression.Frontiers in bioscience (Landmark edition) · 2025Review
- Applications of Limonene in Neoplasms and Non-Neoplastic Diseases.International journal of molecular sciences · 2025Review
- MEBOCOST maps metabolite-mediated intercellular communications using single-cell RNA-seq.Nucleic acids research · 2025Article
Corrections and comments
- Update ofEGFR2023
Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
The limited efficacy of currently approved immunotherapies in EGFR-driven lung adenocarcinoma (LUAD) underscores the need to better understand alternative mechanisms governing local immunosuppression to fuel novel therapies. Elevated surfactant and GM-CSF secretion from the transformed epithelium induces tumor-associated alveolar macrophage (TA-AM) proliferation, which supports tumor growth by rewiring inflammatory functions and lipid metabolism. TA-AM properties are driven by increased GM-CSF-PPARγ signaling and inhibition of airway GM-CSF or PPARγ in TA-AMs suppresses cholesterol efflux to tumor cells, which impairs EGFR phosphorylation and restrains LUAD progression. In the absence of TA-AM metabolic support, LUAD cells compensate by increasing cholesterol synthesis, and blocking PPARγ in TA-AMs simultaneous with statin therapy further suppresses tumor progression and increases proinflammatory immune responses. These results reveal new therapeutic combinations for immunotherapy-resistant EGFR-mutant LUADs and demonstrate how cancer cells can metabolically co-opt TA-AMs through GM-CSF-PPARγ signaling to provide nutrients that promote oncogenic signaling and growth. SIGNIFICANCE: Alternate strategies harnessing anticancer innate immunity are required for lung cancers with poor response rates to T cell-based immunotherapies. This study identifies a targetable, mutually supportive, metabolic relationship between macrophages and transformed epithelium, which is exploited by tumors to obtain metabolic and immunologic support to sustain proliferation and oncogenic signaling.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.