ArticleNature immunology2025
Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer.
Article in Nature immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Cancer associated fibroblast-T cell crosstalk promotes purinergic synthesis in non-small cell lung cancer (NSCLC).Oncoimmunology · 2026Article
- Glutamine metabolism in health and disease.Signal transduction and targeted therapy · 2026Review
- Vitamin B5 supports anti-PD1 response in HER2-positive gastric cancer and enhances interaction between naïve B cells and T cells.Nature communications · 2026Article
- An siENPP1-Delivering Bimetallic MOF Nanocomplex Enables Triple Activation of the cGAS-STING Pathway for Synergistic Triple-Negative Breast Cancer Therapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Engineering an AIEgen-based platform integrating CRISPR/Cas9 to remodel the tumor microenvironment and reinforce photo-immunotherapy against glioblastom.Signal transduction and targeted therapy · 2026Article
- Solute carrier transporters as metabolic gatekeepers in tumor-microenvironment crosstalk.Acta pharmacologica Sinica · 2026Review
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- Advances in artificial metabzymes for macrophage polarization in tumor metabolic immunotherapy.Materials today. Bio · 2026Article
- Synergistic effects of HDAC inhibitor tucidinostat and ENT inhibitor dipyridamole in T-cell malignancies.Scientific reports · 2026Article
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Uridine-Based PET/NIRF Dual-Modality imaging for precision tumor diagnosis and surgery.European journal of nuclear medicine and molecular imaging · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Immune regulatory mechanisms in the tumor microenvironment and their applications in cancer therapy: from basic research to clinical translation.Frontiers in immunology · 2026Review
- The CD73-adenosine axis in melanoma: from multidimensional regulation to precision immunotherapy.Frontiers in immunology · 2026Review
- Nanosystem-Mediated Intercellular Crosstalk Modulation in the Tumor Microenvironment for Enhanced Cancer Immunotherapy.Drug design, development and therapy · 2026Review
- Comprehensive Exploration of NOTCH2NLA Across Cancers and Its Potential Roles in Prognosis and Immune System Interactions.Current medicinal chemistry · 2026Article
- Targeting immunometabolism in cancer through pharmacological and lifestyle interventions.PLoS biology · 2026Review
- Harnessing the immune system: future directions in cancer immunotherapy.Frontiers in immunology · 2026Review
- Adenosine Triggers an ADK-Dependent Intracellular Signaling Pathway Interacts PFKFB3-Mediated Glycolytic Metabolism to Promote Newly Formed Myofibers Development.International journal of molecular sciences · 2025Article
- CD39 and CD73: biological functions, diseases and therapy.Molecular biomedicine · 2025Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
The benefit of immune checkpoint blockade for cancer therapy is limited to subsets of patients because of factors including the accumulation of immunosuppressive metabolites, such as adenosine, within tumors. Pharmacological inhibition of adenosine generation and signaling is an active area of clinical investigation, but only limited clinical benefit has been reported. Here, we show that adenosine suppresses anti-cancer T cell responses following uptake into activated T cells by equilibrative nucleoside transporter 1 (ENT1) and inhibition of de novo pyrimidine nucleotide synthesis. We identify EOS301984 as a potent ENT1 antagonist that restores pyrimidine levels in activated T cells in adenosine-rich environments, resulting in enhanced tumor cell killing by memory T cells and increased ex vivo expansion of functional human tumor-infiltrating lymphocytes. A combination of EOS301984 with anti-PD-1 led to synergistic control of tumor growth in a humanized mouse model of triple-negative breast cancer. ENT1 inhibition, therefore, augments anti-cancer immune responses through the restoration of pyrimidine nucleotide synthesis in T cells suppressed by adenosine.
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