ArticleScience advances2024
NF-κB and TET2 promote macrophage reprogramming in hypoxia that overrides the immunosuppressive effects of the tumor microenvironment.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Impaired Glycolysis Leads to Defective Efferocytosis and Impaired Plaque Resolution inCirculation · 2026Article
- Biomolecular Condensates Integrate Transcriptional and Epigenetic Responses to Hypoxia.International journal of molecular sciences · 2026Review
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- Nanozyme-Mediated Cellular and Microenvironmental Metabolic Reprogramming for Boosting Cancer Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- Exposure to electronic cigarette aerosols triggers alterations in genomic DNA methylation that impacts cancer pathways in mice.Inhalation toxicology · 2026Article
- Combined targeting of VISTA and sorafenib activates T cell-mediated anti-tumor immunity via the NF-κB/TNF axis in hepatocellular carcinoma.BMC medicine · 2026Article
- ATP-Responsive Bimetallic Metal-Organic Frameworks Amplify Oxidative Stress in the Tumor Microenvironment for Synergistic Chemo-Immunotherapy.Journal of functional biomaterials · 2026Article
- HIF-1α suppresses SNPH expression to facilitate liver metastasis of colorectal cancer through regulating mitochondrial dynamics and filopodia formation.Cell death & disease · 2026Article
- TET2 in epigenetic control of immune cells: Implications for inflammatory responses and age-related pathologies.The Journal of biological chemistry · 2026Review
- HSP72-AMPK axis mitigates hypoxia-induced cellular senescence to promote colorectal cancer development.Molecular and cellular biochemistry · 2026Article
- IRG1-itaconate axis in immunometabolism: mechanistic roles and therapeutic potential in inflammatory diseases.Frontiers in immunology · 2026Review
- Granulomatous mastitis: from localized inflammation to systemic immune-mediated disorder.Frontiers in medicine · 2026Review
- The metabolic environment within solid tumors drives a complex crosstalk between macrophages and NK cells.Frontiers in immunology · 2026Review
- Inhibiting OAS3 suppresses the development of clear cell renal cell carcinoma by reducing cell proliferation and altering the tumor immune microenvironment.American journal of translational research · 2026Article
- NLRP12 in cancer: a context-dependent regulator of tumor progression, immunity, and metabolism.Frontiers in oncology · 2026Review
- Macrophage-based therapeutic strategies in glioblastoma: advancements in drug delivery and immunotherapy.Frontiers in oncology · 2026Review
- Association Between Atopic Dermatitis and Colorectal Cancer Risk: A Korean Population-Based Study.Biomedicines · 2025Article
- Macrophages: sentinels, warriors, and healers.Human molecular genetics · 2025Review
- DNA methylation and transcription factor-driven immune subtypes in ovarian cancer.Discover oncology · 2025Article
- Single-cell profiling uncovers the intricate pathological niche diversity in brain, lymph node, bone, and adrenal metastases of lung cancer.Discover oncology · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages orchestrate tissue homeostasis and immunity. In the tumor microenvironment (TME), macrophage presence is largely associated with poor prognosis because of their reprogramming into immunosuppressive cells. We investigated the effects of hypoxia, a TME-associated feature, on the functional, epigenetic, and transcriptional reprogramming of macrophages and found that hypoxia boosts their immunogenicity. Hypoxic inflammatory macrophages are characterized by a cluster of proinflammatory genes undergoing ten-eleven translocation-mediated DNA demethylation and overexpression. These genes are regulated by NF-κB, while HIF1α dominates the transcriptional reprogramming, demonstrated through ChIP-seq and pharmacological inhibition. In bladder and ovarian carcinomas, hypoxic inflammatory macrophages are enriched in immune-infiltrated tumors, correlating with better patient prognoses. Coculture assays and cell-cell communication analyses support that hypoxic-activated macrophages enhance T cell-mediated responses. The NF-κB-associated hypomethylation signature is displayed by a subset of hypoxic inflammatory macrophages, isolated from ovarian tumors. Our results challenge paradigms regarding the effects of hypoxia on macrophages and highlight actionable target cells to modulate anticancer immune responses.
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