ArticleJournal of the National Cancer Institute2023
Improving combination therapies: targeting A2B-adenosine receptor to modulate metabolic tumor microenvironment and immunosuppression.
Article in Journal of the National Cancer Institute, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- The ATP-adenosine axis as a driver of tumor-associated macrophage reprogramming in colorectal cancer: mechanistic insights into immune evasion and therapeutic vulnerabilities.Purinergic signalling · 2026Review
- First-in-human study of the dual AESMO open · 2026Article
- Enhanced antitumor efficacy of combined targeting of adenosine ACancer immunology, immunotherapy : CII · 2026Article
- Metabolic-Immune Coupling in Urologic Cancers: Macrophage Reprogramming as a Therapeutic Nexus.International journal of biological sciences · 2026Review
- Dual blockade of adenosine AFrontiers in immunology · 2026Article
- Review
- Phase 1 dose escalation trial of the selective adenosine A2B antagonist PBF-1129 in patients with metastatic non-small cell lung cancer.Investigational new drugs · 2025Article
- Non-Canonical Functions of Adenosine Receptors: Emerging Roles in Metabolism, Immunometabolism, and Epigenetic Regulation.International journal of molecular sciences · 2025Review
- Deciphering adenosine signaling in hepatocellular carcinoma: Pathways, prognostic models, and therapeutic implications.Clinical and molecular hepatology · 2025Review
- Therapeutic potential of adenosine receptor modulators in cancer treatment.RSC advances · 2025Review
- Adenosine ACells · 2025Article
- The progress and prospects of targeting the adenosine pathway in cancer immunotherapy.Biomarker research · 2025Review
- APurinergic signalling · 2025Review
- Line-Shifting Triarylmethyl Radicals for Imaging of Enzyme Activity Using Overhauser-Enhanced Magnetic Resonance Imaging: Application to Alkaline Phosphatase.Chemical & biomedical imaging · 2025Article
- Enzymatic and microenvironmental regulation in adenosine metabolism-mediated immunosuppression.Frontiers in immunology · 2025Review
- CD39Frontiers in oncology · 2025Review
- The Adenosinergic Pathway in Non-Small Cell Lung Cancer.Cancers · 2024Review
- A novel and selective fluorescent ligand for the study of adenosine APharmacology research & perspectives · 2024Article
- Current Understanding of the Role of Adenosine Receptors in Cancer.Molecules (Basel, Switzerland) · 2024Review
- Adenosine and Its Receptors in the Pathogenesis and Treatment of Inflammatory Skin Diseases.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
33 authors at 9 institutions in 4 countries.
Funding
Abstract
backgroundWe investigated the role of A2B-adenosine receptor in regulating immunosuppressive metabolic stress in the tumor microenvironment. Novel A2B-adenosine receptor antagonist PBF-1129 was tested for antitumor activity in mice and evaluated for safety and immunologic efficacy in a phase I clinical trial of patients with non-small cell lung cancer.
methodsThe antitumor efficacy of A2B-adenosine receptor antagonists and their impact on the metabolic and immune tumor microenvironment were evaluated in lung, melanoma, colon, breast, and epidermal growth factor receptor-inducible transgenic cancer models. Employing electron paramagnetic resonance, we assessed changes in tumor microenvironment metabolic parameters, including pO2, pH, and inorganic phosphate, during tumor growth and evaluated the immunologic effects of PBF-1129, including its pharmacokinetics, safety, and toxicity, in patients with non-small cell lung cancer.
resultsLevels of metabolic stress correlated with tumor growth, metastasis, and immunosuppression. Tumor interstitial inorganic phosphate emerged as a correlative and cumulative measure of tumor microenvironment stress and immunosuppression. A2B-adenosine receptor inhibition alleviated metabolic stress, downregulated expression of adenosine-generating ectonucleotidases, increased expression of adenosine deaminase, decreased tumor growth and metastasis, increased interferon γ production, and enhanced the efficacy of antitumor therapies following combination regimens in animal models (anti-programmed cell death 1 protein vs anti-programmed cell death 1 protein plus PBF-1129 treatment hazard ratio = 11.74 [95% confidence interval = 3.35 to 41.13], n = 10, P < .001, 2-sided F test). In patients with non-small cell lung cancer, PBF-1129 was well tolerated, with no dose-limiting toxicities; demonstrated pharmacologic efficacy; modulated the adenosine generation system; and improved antitumor immunity.
conclusionsData identify A2B-adenosine receptor as a valuable therapeutic target to modify metabolic and immune tumor microenvironment to reduce immunosuppression, enhance the efficacy of immunotherapies, and support clinical application of PBF-1129 in combination therapies.
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