ArticleScience advances2023
Hypoxia-inducible factor orchestrates adenosine metabolism to promote liver cancer development.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 53 citations in OpenAlex.
- Unraveling the tapestry: Lessons from multi-omics and spatial biology in hepatocellular cancer.Hepatology (Baltimore, Md.) · 2026Review
- Beyond apoptosis: nanomedicine enabled reprogramming of tumor cell death for next-generation radiosensitization.Journal of nanobiotechnology · 2026Review
- Piezobiomimetic delivery nanosystem converts cold tumors to hot by parallel PANoptosis/STING activation in hepatocellular carcinoma.Science advances · 2026Article
- Cellular mechanometabolism: stimuli and implications.EMBO reports · 2026Review
- Illuminating the path to oncolysis: rise of microbial phototherapy.Journal of nanobiotechnology · 2026Review
- Enhancing Exercise Performance Under Hypoxia: A Network Meta-Analysis and Animal Experimental Validation of Plant Bioactive Compounds.Nutrients · 2026Article
- Therapy-induced remodeling of the tumor immune microenvironment: Mechanistic insights and implications for immunotherapy.Chinese medical journal · 2026Review
- Nutritional modulation of metabolic signaling within the tumor microenvironment for cancer therapy.Molecular and cellular biochemistry · 2026Review
- Multifunctional Nano Immunostimulant: Overcoming Immunosuppressive Microenvironment for Antitumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adenosine metabolic clearance maintains liver homeostasis by licensing arginine methylation of RIPK1.The Journal of experimental medicine · 2026Article
- Photodynamically Sensitized Mitochondrial-Damage Amplification Strategy Promotes Pyroptosis-Induced Immunotherapy of Osteosarcoma.Biomaterials research · 2026Article
- Hypoxia-driven tumor immune escape: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- FUBP3 mediates MXI1 stability to silence RRAS and hinder MAPK signaling in acute megakaryoblastic leukemia progression.Cancer immunology, immunotherapy : CII · 2025Article
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation.Trends in biochemical sciences · 2025Review
- Non-Canonical Functions of Adenosine Receptors: Emerging Roles in Metabolism, Immunometabolism, and Epigenetic Regulation.International journal of molecular sciences · 2025Review
- Hypoxia-mediated HES4 promotes the proliferation and motility of hepatocellular carcinoma cell by enhancing COL4A2 transcription.Discover oncology · 2025Article
- Deciphering adenosine signaling in hepatocellular carcinoma: Pathways, prognostic models, and therapeutic implications.Clinical and molecular hepatology · 2025Review
- Effect and mechanism of PYCR1 on biological function of hepatocellular carcinoma cells under hypoxia.Discover oncology · 2025Article
- Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Review
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-induced adenosine creates an immunosuppressive tumor microenvironment (TME) and dampens the efficacy of immune checkpoint inhibitors (ICIs). We found that hypoxia-inducible factor 1 (HIF-1) orchestrates adenosine efflux through two steps in hepatocellular carcinoma (HCC). First, HIF-1 activates transcriptional repressor MXI1, which inhibits adenosine kinase (ADK), resulting in the failure of adenosine phosphorylation to adenosine monophosphate. This leads to adenosine accumulation in hypoxic cancer cells. Second, HIF-1 transcriptionally activates equilibrative nucleoside transporter 4, pumping adenosine into the interstitial space of HCC, elevating extracellular adenosine levels. Multiple in vitro assays demonstrated the immunosuppressive role of adenosine on T cells and myeloid cells. Knockout of ADK in vivo skewed intratumoral immune cells to protumorigenic and promoted tumor progression. Therapeutically, combination treatment of adenosine receptor antagonists and anti-PD-1 prolonged survival of HCC-bearing mice. We illustrated the dual role of hypoxia in establishing an adenosine-mediated immunosuppressive TME and offered a potential therapeutic approach that synergizes with ICIs in HCC.
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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.