ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Selective inhibition of KCa3.1 channels mediates adenosine regulation of the motility of human T cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. 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.
- CD8⁺ T Cell infiltration and spatial organization in cancer: mechanisms, barriers, and therapeutic strategies.Molecular biomedicine · 2026Review
- Potassium channels as an ionic checkpoint in tumor immunity.Frontiers in pharmacology · 2026Review
- KCa3.1 channels regulate the tumor infiltration of functionally competent NK cells in head and neck cancer.Scientific reports · 2025Article
- Nanomaterials-mediated adenosine pathway inhibition for strengthening cancer immunotherapy.Theranostics · 2025Review
- Metabolic gatekeepers: harnessing tumor-derived metabolites to optimize T cell-based immunotherapy efficacy in the tumor microenvironment.Cell death & disease · 2024Review
- SubvertingBiology · 2024Review
- The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies.Acta pharmaceutica Sinica. B · 2024Review
- Activity of Potassium Channels in CD8International journal of molecular sciences · 2024Article
- Intracellular acidity impedes KCa3.1 activation by Riluzole and SKA-31.Frontiers in pharmacology · 2024Article
- Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Review
- Tumor-intrinsic metabolic reprogramming and how it drives resistance to anti-PD-1/PD-L1 treatment.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Adenosine A2a Receptor Antagonism Restores Additive Cytotoxicity by Cytotoxic T Cells in Metabolically Perturbed Tumors.Cancer immunology research · 2022Article
- How the Potassium Channel Response of T Lymphocytes to the Tumor Microenvironment Shapes Antitumor Immunity.Cancers · 2022Review
- Midazolam's Effects on Delayed-Rectifier KInternational journal of molecular sciences · 2021Article
- Targeted knockdown of the adenosine AMolecular therapy. Methods & clinical development · 2021Article
- Immune Checkpoint Inhibitors Regulate KFrontiers in pharmacology · 2021Article
- KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways.Cancer biomarkers : section A of Disease markers · 2021Article
- Ion Channel Dysregulation in Head and Neck Cancers: Perspectives for Clinical Application.Reviews of physiology, biochemistry and pharmacology · 2021Review
- PD1 blockade enhances KJournal for immunotherapy of cancer · 2020Article
- pH-Channeling in Cancer: How pH-Dependence of Cation Channels Shapes Cancer Pathophysiology.Cancers · 2020Review
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Authors and funding
8 authors.
Funding
Abstract
Adenosine, a purine nucleoside, is present at high concentrations in tumors, where it contributes to the failure of immune cells to eliminate cancer cells. The mechanisms responsible for the immunosuppressive properties of adenosine are not fully understood. We tested the hypothesis that adenosine's immunosuppressive functions in human T lymphocytes are in part mediated via modulation of ion channels. The activity of T lymphocytes relies on ion channels. KCa3.1 and Kv1.3 channels control cytokine release and, together with TRPM7, regulate T cell motility. Adenosine selectively inhibited KCa3.1, but not Kv1.3 and TRPM7, in activated human T cells. This effect of adenosine was mainly mediated by A2A receptors, as KCa3.1 inhibition was reversed by SCH58261 (selective A2A receptor antagonist), but not by MRS1754 (A2B receptor antagonist), and it was mimicked by the A2A receptor agonist CGS21680. Furthermore, it was mediated by the cAMP/protein kinase A isoform (PKAI) signaling pathway, as adenylyl-cyclase and PKAI inhibition prevented adenosine effect on KCa3.1. The functional implication of the effect of adenosine on KCa3.1 was determined by measuring T cell motility on ICAM-1 surfaces. Adenosine and CGS21680 inhibited T cell migration. Comparable effects were obtained by KCa3.1 blockade with TRAM-34. Furthermore, the effect of adenosine on cell migration was abolished by pre-exposure to TRAM-34. Additionally, adenosine suppresses IL-2 secretion via KCa3.1 inhibition. Our data indicate that adenosine inhibits KCa3.1 in human T cells via A2A receptor and PKAI, thereby resulting in decreased T cell motility and cytokine release. This mechanism is likely to contribute to decreased immune surveillance in solid tumors.
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