ArticleCancer immunology research2024
Intracellular K+ Limits T-cell Exhaustion and Preserves Antitumor Function.
Article in Cancer immunology research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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
11 citing papers in PubMed, 13 citations in OpenAlex.
- Potassium channels as an ionic checkpoint in tumor immunity.Frontiers in pharmacology · 2026Review
- LncDARS-AS1 Regulates ATP1A1 Stability and Enhances NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- Downregulation of the HCN1 Channel Alleviates Anxiety- and Depression-Like Behaviors in Mice With Cerebral Ischemia-Reperfusion Injury by Suppressing the NLRP3 Inflammasome.Journal of the American Heart Association · 2025Article
- High Extracellular KEuropean journal of immunology · 2025Article
- Review
- GPR37-enhanced ubiquitination of ATP1A1 inhibits tumor progression and radiation resistance in esophageal squamous cell carcinoma.Cell death & disease · 2024Article
- Targeting mitochondria: restoring the antitumor efficacy of exhausted T cells.Molecular cancer · 2024Review
- Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity.Nature immunology · 2024Article
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- CD8+ T Cells Keep Their (K+)urrency for Function.Cancer immunology research · 2024Article
Corrections and comments
- Commented on by
- Update ofIntracellular K2023
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
T cells are often compromised within cancers, allowing disease progression. We previously found that intratumoral elevations in extracellular K+, related to ongoing cell death, constrained CD8+ T-cell Akt-mTOR signaling and effector function. To alleviate K+-mediated T-cell dysfunction, we pursued genetic means to lower intracellular K+. CD8+ T cells robustly and dynamically express the Na+/K+ ATPase, among other K+ transporters. CRISPR-Cas9-mediated disruption of the Atp1a1 locus lowered intracellular K+ and elevated the resting membrane potential (i.e., Vm, Ψ). Despite compromised Ca2+ influx, Atp1a1-deficient T cells harbored tonic hyperactivity in multiple signal transduction cascades, along with a phenotype of exhaustion in mouse and human CD8+ T cells. Provision of exogenous K+ restored intracellular levels in Atp1a1-deficient T cells and prevented damaging levels of reactive oxygen species (ROS), and both antioxidant treatment and exogenous K+ prevented Atp1a1-deficient T-cell exhaustion in vitro. T cells lacking Atp1a1 had compromised persistence and antitumor activity in a syngeneic model of orthotopic murine melanoma. Translational application of these findings will require balancing the beneficial aspects of intracellular K+ with the ROS-dependent nature of T-cell effector function. See related Spotlight by Banuelos and Borges da Silva, p. 6.
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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.