ArticleCancer immunology, immunotherapy : CII2021
Comparative analysis of the tumor immune-microenvironment of primary and brain metastases of non-small-cell lung cancer reveals organ-specific and EGFR mutation-dependent unique immune landscape.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Risk factors for brain metastasis in lung cancer: an umbrella review of systematic reviews and meta-analyses.BMJ open · 2025Pooled it
- Immune-related pan-cancer gene expression signatures of patient survival revealed by NanoString-based analyses.PloS one · 2023Pooled it
- Anti-PD-1 plus anti-CTLA-4 blockade overcomes immune exclusion in NSCLC brain metastases by enhancing CD8Nature communications · 2026Article
- Magnetic resonance imaging characteristics of brain metastases from lung cancer.Quantitative imaging in medicine and surgery · 2026Article
- Coordinated Multicellular Immune Programs and Drug Targets Revealed by Single-Cell Analysis in Driver-Mutated NSCLC.International journal of molecular sciences · 2026Article
- Metastatic breast cancer in primary lung cancer with compoundOncology letters · 2026Article
- Identification of altered immune landscape at single-cell resolution in NSCLC brain metastasis and its association with poor immune checkpoint inhibitor responses.Nature communications · 2026Article
- MET alterations are enriched in lung adenocarcinoma brain metastases, defining a distinct biologic subtype.The Journal of clinical investigation · 2026Article
- Diversity and function of tumor-associated macrophages in brain metastases: mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Lipocalin-2 drives brain metastatic progression through reciprocal tumor-microenvironment interactions in lung cancer.Signal transduction and targeted therapy · 2025Article
- Single-cell and spatial transcriptome landscapes reveal the spatial immune defense pattern shared by primary and brain metastatic lung adenocarcinoma.Journal of thoracic disease · 2025Article
- [Research Progress on the Mechanism of Gut Microbiota Influencing Lung Cancer Brain Metastasis via the Brain-gut Axis].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- Molecular evolution of central nervous system metastasis and therapeutic implications.Trends in molecular medicine · 2025Review
- Targeting adenosine enhances immunotherapy in MSS colorectal cancer with EGFRvIII mutation.Journal for immunotherapy of cancer · 2025Article
- Progress in personalized immunotherapy for patients with brain metastasis.NPJ precision oncology · 2025Review
- The immune landscape in brain metastasis.Neuro-oncology · 2025Review
- Review
- Key genes associated with brain metastasis in non-small cell lung cancer: novel insights from bioinformatics analysis.Frontiers in bioinformatics · 2025Article
- Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2024Review
- Proteomics-based Model for Predicting the Risk of Brain Metastasis in Patients with Resected Lung Adenocarcinoma carrying the EGFR Mutation.International journal of medical sciences · 2024Article
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Authors and funding
8 authors at 1 institution in 4 countries.
Funding
Abstract
backgroundTo evaluate the characteristics of the tumor immune-microenvironment in brain metastases of non-small-cell lung cancer (NSCLC), we investigated the immunophenotype of primary NSCLC and its brain metastasis.
methodsExpression profiling of 770 immune-related genes in 28 tissues from primary and brain metastases of NSCLC was performed using the NanoString nCounter PanCancer Immune Profiling Panel. The immune cell profiles were validated by immunohistochemistry of 42 matched samples.
resultsBased on unsupervised clustering and principal component analysis of the immune-related gene expression profile, tumors were primarily clustered according to the involved organ and further grouped according to the EGFR mutation status. Fifty-four genes were significantly differentially expressed between primary and brain metastatic tumors. Clustering using these genes showed that tumors harboring mutated EGFR tended to be grouped together in the brain. Pathway analysis revealed that various immune-related functions involving immune regulation, T cell activity, and chemokines were enriched in primary tumors compared to brain metastases. Diverse immune-related pathways were upregulated in brain metastases of EGFR-mutated compared to EGFR-wild-type adenocarcinoma, but not in primary tumors. The interferon-γ-related gene signature was significantly decreased in brain metastases. The anti-inflammatory markers TOLLIP and HLA-G were upregulated in brain metastases. The proportions of most immune cell subsets were decreased in brain metastases, but those of macrophages and CD56dim-NK-cells were increased, as was the ratios of CD163
conclusionsOur findings illustrate the immune landscape of brain metastases from NSCLC and reveal potential therapeutic strategies targeting cellular and non-cellular components of the tumor immune-microenvironment.
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