ArticleCancer immunology, immunotherapy : CII2008
Cooperation of adenosine and prostaglandin E2 (PGE2) in amplification of cAMP-PKA signaling and immunosuppression.
Article in Cancer immunology, immunotherapy : CII, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 65 citations in OpenAlex.
- GPCR Biased Signaling in Cancer.Handbook of experimental pharmacology · 2026Review
- Protein kinase A and local signaling in cancer.The Biochemical journal · 2024Review
- Chimeric antigen receptor T cells therapy in solid tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Modulation of natural killer cell exhaustion in the lungs: the key components from lung microenvironment and lung tumor microenvironment.Frontiers in immunology · 2023Review
- Research progress of treatment of functional dyspepsia with traditional Chinese medicine compound based on cell signal pathway.Frontiers in pharmacology · 2022Review
- Immunosuppressive metabolites in tumoral immune evasion: redundancies, clinical efforts, and pathways forward.Journal for immunotherapy of cancer · 2021Review
- CAR-T cells: Early successes in blood cancer and challenges in solid tumors.Acta pharmaceutica Sinica. B · 2021Review
- Review
- Adoptive T cell therapy: Boosting the immune system to fight cancer.Seminars in immunology · 2020Review
- Prostaglandin E2 Regulates Activation of Mouse Peritoneal Macrophages by Staphylococcus aureus through Toll-Like Receptor 2, Toll-Like Receptor 4, and NLRP3 Inflammasome Signaling.Journal of innate immunity · 2020Article
- The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities.Frontiers in immunology · 2020Review
- Critical role of kinase activity of hematopoietic progenitor kinase 1 in anti-tumor immune surveillance.PloS one · 2019Article
- Influence of the Tumor Microenvironment on NK Cell Function in Solid Tumors.Frontiers in immunology · 2019Review
- Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function.Frontiers in immunology · 2019Review
- Chimeric antigen receptor T cell (CAR-T) immunotherapy for solid tumors: lessons learned and strategies for moving forward.Journal of hematology & oncology · 2018Review
- MicroRNA: Dynamic Regulators of Macrophage Polarization and Plasticity.Frontiers in immunology · 2017Review
- Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications.Frontiers in immunology · 2017Review
- Augmentation of CAR T-cell Trafficking and Antitumor Efficacy by Blocking Protein Kinase A Localization.Cancer immunology research · 2016Article
- Methotrexate up-regulates ecto-5'-nucleotidase/CD73 and reduces the frequency of T lymphocytes in the glioblastoma microenvironment.Purinergic signalling · 2016Article
- Chimeric antigen receptor T-cell therapy for solid tumors.Molecular therapy oncolytics · 2016Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionWe hypothesize that adenosine and PGE2 could have a complementary immunosuppressive effect that is mediated via common cAMP-PKA signaling. MATERIALS AND
methodsTo test this hypothesis, the effect of adenosine and PGE2 on the cytotoxic activity and cytokine production of lymphokine activated killer (LAK) cells was investigated.
resultsPGE2 and adenosine inhibited LAK cells cytotoxic activity and production of INF-gamma, GM-CSF and TNF-alpha. In combination they showed substantially higher inhibition than each modality used alone. Using agonists and antagonists specific for PGE2 and adenosine receptors we found that cooperation of PGE2 and adenosine in their inhibitory effects are mediated via EP2 and A2A receptors, respectively. LAK cells have 35-fold higher expression of EP2 than A2A. Combined PGE2 and adenosine treatment resulted in augmentation of cAMP production, PKA activity, CREB phosphorylation and inhibition of Akt phosphorylation. Wortmannin and LY294002 enhanced the suppressive effects of adenosine and PGE2. In contrast, Rp-8-Br-cAMPS, an inhibitor of PKA type I blocked their immunosuppressive effects, suggesting that the inhibitory effects of PGE2 and adenosine are mediated via common pathway with activation of cAMP-PKA and inhibition of Akt.
conclusionIn comparison to other immunosuppressive molecules (TGF-beta and IL-10), adenosine and PGE2 are unique in their ability to inhibit the executive function of highly cytotoxic cells. High intratumor levels of adenosine and PGE2 could protect tumor from immune-mediated destruction by inactivation of the tumor infiltrating functionally active immune cells.
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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.