ArticleCancer research2020
Hypoxia Induces Transcriptional and Translational Downregulation of the Type I IFN Pathway in Multiple Cancer Cell Types.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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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.
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Who cites it
64 citing papers in PubMed, 78 citations in OpenAlex.
- HIF-1-mediated PPME1 expression promotes breast cancer progression via AKT activation and β-catenin recruitment.The Journal of clinical investigation · 2026Article
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- Variants ofLife science alliance · 2026Article
- Formic acid released by intratumoralActa pharmaceutica Sinica. B · 2026Article
- Hypoxia Differentially Regulates Ferroptosis Sensitivity and Tumor Cell-Intrinsic Type I Interferon Signaling in Pancreatic Ductal Adenocarcinoma Cells.International journal of molecular sciences · 2026Article
- The role of HIF-1α in innate immune mechanisms and autoimmunity: A double-edged sword.The Journal of biological chemistry · 2026Review
- Spatial Chromatin Accessibility Analysis of Intratumor Heterogeneity in Breast Cancer.Genomics, proteomics & bioinformatics · 2026Article
- Single-cell and spatial transcriptome profiling identifies cellular heterogeneity and immunosuppressive tumor microenvironment in inflammatory breast cancer.Journal of advanced research · 2026Article
- Hypoxia induced VEGF secretion promotes resistance to bispecific T-cell engagers.Signal transduction and targeted therapy · 2025Article
- Carbonic Anhydrase 3 Overexpression Modulates Signalling Pathways Associated with Cellular Stress Resilience and Proteostasis.International journal of molecular sciences · 2025Article
- Hypoxia increases susceptibility of human intestinal epithelial cells to rotavirus infection through repression of interferon induction.Gut microbes · 2025Article
- ADAR1 expression in different cancer cell lines and its change under heat shock.Journal of applied genetics · 2025Article
- ADAR1-mediated RNA editing in breast cancer: molecular mechanisms and therapeutic implications.Medical oncology (Northwood, London, England) · 2025Review
- Analysis of an engineered organoid model of pancreatic cancer identifies hypoxia as a contributing factor in determining transcriptional subtypes.Scientific reports · 2025Article
- Article
- Article
- How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia.Nature reviews. Immunology · 2025Review
- InfoScan: A New Transcript Identification Tool Based on scRNA-Seq and Its Application in Glioblastoma.International journal of molecular sciences · 2025Article
- FAT1 knockdown enhances the CSC properties of HNSCC through p-CaMKII-mediated inactivation of the IFN pathway.International journal of biological sciences · 2025Article
- CAR-M therapy in the era of tumor immunotherapy: current research progress and engineering strategies.Frontiers in immunology · 2025Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Hypoxia is a common phenomenon in solid tumors and is strongly linked to hallmarks of cancer. Recent evidence has shown that hypoxia promotes local immune suppression. Type I IFN supports cytotoxic T lymphocytes by stimulating the maturation of dendritic cells and enhancing their capacity to process and present antigens. However, little is known about the relationship between hypoxia and the type I IFN pathway, which comprises the sensing of double-stranded RNA and DNA (dsRNA/dsDNA) followed by IFNα/β secretion and transcriptional activation of IFN-stimulated genes (ISG). In this study, we determined the effects of hypoxia on the type I IFN pathway in breast cancer and the mechanisms involved. In cancer cell lines and xenograft models, mRNA and protein expressions of the type I IFN pathway were downregulated under hypoxic conditions. This pathway was suppressed at each level of signaling, from the dsRNA sensors RIG-I and MDA5, the adaptor MAVS, transcription factors IRF3, IRF7, and STAT1, and several ISG including RIG-I, IRF7, STAT1, and ADAR-p150. Importantly, IFN secretion was reduced under hypoxic conditions. HIF1α- and HIF2α-mediated regulation of gene expression did not explain most of the effects. However, ATAC-seq data revealed in hypoxia that peaks with STAT1 and IRF3 motifs had decreased accessibility. Collectively, these results indicate that hypoxia leads to an overall downregulation of the type I IFN pathway due to repressed transcription and lower chromatin accessibility in an HIF1/2α-independent manner, which could contribute to immunosuppression in hypoxic tumors. SIGNIFICANCE: These findings characterize a new mechanism of immunosuppression by hypoxia via downregulation of the type I IFN pathway and its autocrine/paracrine effects on tumor growth.
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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.