ArticleNature communications2022
Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 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
118 citing papers in PubMed, 159 citations in OpenAlex.
- Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).The Journal of clinical investigation · 2026Trial
- Dexamethasone prophylaxis protects from acute high-altitude illness by modifying the peripheral blood mononuclear cell inflammatory transcriptome.Bioscience reports · 2023Trial
- Review
- High ZFP36 Family Expression in Exhausted T Cells Is Associated With Impaired Antitumor Effector Function.Cancer science · 2026Article
- Review
- Epigenetic Plasticity in Triple-Negative Breast Cancer: Mechanisms of Therapy Resistance, Biomarkers, and Therapeutic Vulnerabilities.Biomedicines · 2026Review
- Physical Exercise in Immunotherapy.Sports medicine - open · 2026Review
- Fast-Food Component-Induced Epigenetic Modifications Modulate Immunotherapy in Metastatic Breast Cancer.ACS omega · 2026Article
- Aminated fullerene-based nanoplatform enables synergistic VEGFR2-targeted anti-angiogenesis and tumor immunotherapy.Bioactive materials · 2026Article
- A feedback mechanism between E3 ligase RNF122 and HIF-1α inhibits aggressive behavior in breast cancer.Oncogene · 2026Article
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- PSPH Promotes Hepatocellular Carcinoma Progression by Upregulating HIF-1α and Is Regulated by LncRNA GSEC/miR-101-3p.Current issues in molecular biology · 2026Article
- FOSL2 drives transcriptional activation of super‑enhancer-regulatedMolecular medicine reports · 2026Article
- Article
- Honokiol and Its Emerging Role in Breast Cancer Therapy.Cancers · 2026Review
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Ultrasound-targeted microbubble cavitation enhances anti-PD-L1 therapy in TNBC via eNOS-mediated reoxygenation.JCI insight · 2026Article
- Review
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- Targeting conserved domains of hypoxia-inducible factors for cancer therapy.The Journal of experimental medicine · 2026Article
58 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
19 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hypoxic tumor microenvironment has been implicated in immune escape, but the underlying mechanism remains elusive. Using an in vitro culture system modeling human T cell dysfunction and exhaustion in triple-negative breast cancer (TNBC), we find that hypoxia suppresses immune effector gene expression, including in T and NK cells, resulting in immune effector cell dysfunction and resistance to immunotherapy. We demonstrate that hypoxia-induced factor 1α (HIF1α) interaction with HDAC1 and concurrent PRC2 dependency causes chromatin remolding resulting in epigenetic suppression of effector genes and subsequent immune dysfunction. Targeting HIF1α and the associated epigenetic machinery can reverse the immune effector dysfunction and overcome resistance to PD-1 blockade, as demonstrated both in vitro and in vivo using syngeneic and humanized mice models. These findings identify a HIF1α-mediated epigenetic mechanism in immune dysfunction and provide a potential strategy to overcome immune resistance in TNBC.
Indexed as
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.