ArticleInternational immunology2014
Hypoxia-induced and A2A adenosine receptor-independent T-cell suppression is short lived and easily reversible.
Article in International immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Nucleotide signaling in neutrophils: a key player in cancer dynamics.Purinergic signalling · 2026Review
- Metabolic Profiling to Assess Response to Targeted and Immune Therapy in Melanoma.International journal of molecular sciences · 2024Review
- Article
- Rewiring the T cell-suppressive cytokine landscape of the tumor microenvironment: a new frontier for precision anti-cancer therapy.Frontiers in immunology · 2024Review
- Hypoxia and the Hypoxia-Inducible Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023Review
- Review
- Differential expression of checkpoint markers in the normoxic and hypoxic microenvironment of glioblastomas.Brain pathology (Zurich, Switzerland) · 2023Article
- Role of CAR T Cell Metabolism for Therapeutic Efficacy.Cancers · 2022Review
- Menstrual blood-derived mesenchymal stem cells attenuate inflammation and improve the mortality of acute liver failure combining with A2AR agonist in mice.Journal of gastroenterology and hepatology · 2021Article
- PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression.Cancers · 2021Review
- Fundamentals of T Cell Metabolism and Strategies to Enhance Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Quantitative Analyses Reveal How Hypoxia Reconfigures the Proteome of Primary Cytotoxic T Lymphocytes.Frontiers in immunology · 2021Article
- Antihypoxic oxygenation agents with respiratory hyperoxia to improve cancer immunotherapy.The Journal of clinical investigation · 2020Review
- The yin and yang functions of extracellular ATP and adenosine in tumor immunity.Cancer cell international · 2020Review
- Targeting Adenosine Receptor Signaling in Cancer Immunotherapy.International journal of molecular sciences · 2018Review
- AJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- The Hypoxia-Adenosine Link during Intestinal Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2018Review
- Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Adenosine-mediated immunosuppression in patients with squamous cell carcinoma of the head and neck.HNO · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Tissue hypoxia plays a key role in establishing an immunosuppressive environment in vivo by, among other effects, increasing the level of extracellular adenosine, which then signals through A2A adenosine receptor (A2AR) to elicit its immunosuppressive effect. Although the important role of the adenosine--A2AR interaction in limiting inflammation has been established, the current study revisited this issue by asking whether hypoxia can also exert its T-cell inhibitory effects even without A2AR. A similar degree of hypoxia-triggered inhibition was observed in wild-type and A2AR-deficient T cells both in vitro and, after exposure of mice to a hypoxic atmosphere, in vivo. This A2AR-independent hypoxic T-cell suppression was qualitatively and mechanistically different from immunosuppression by A2AR stimulation. The A2AR-independent hypoxic immunosuppression strongly reduced T-cell proliferation, while IFN-γ-producing activity was more susceptible to the A2AR-dependent inhibition. In contrast to the sustained functional impairment after A2AR-mediated T-cell inhibition, the A2AR-independent inhibition under hypoxia was short lived, as evidenced by the quick recovery of IFN-γ-producing activity upon re-stimulation. These data support the view that T-cell inhibition by hypoxia can be mediated by multiple mechanisms and that both A2AR and key molecules in the A2AR-independent T-cell inhibition should be targeted to overcome the hypoxia-related immunosuppression in infected tissues and tumors.
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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.