ArticleCancer immunology, immunotherapy : CII2011
Receptor desensitization and blockade of the suppressive effects of prostaglandin E(2) and adenosine on the cytotoxic activity of human melanoma-infiltrating T lymphocytes.
Article in Cancer immunology, immunotherapy : CII, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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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.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Ablation of prostaglandin ENature biomedical engineering · 2026Article
- Nanomaterials Reshaping Tumor Metabolism: A New Frontier to Overcome T Cell Exhaustion.International journal of nanomedicine · 2026Review
- STAT3 signaling is associated with neuroimmune dysregulation in a Dravet syndrome model and pediatric drug-resistant epilepsy.Frontiers in neuroscience · 2026Article
- Tumor Microenvironmental Dynamics in Shaping Resistance to Therapeutic Interventions in Melanoma: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Immune Regulatory Role of Adenosine in the Tumor Microenvironment.International journal of molecular sciences · 2023Review
- Breast Cancer Cell-Derived Adenosine Enhances Generation and Suppressor Function of Human Adaptive Regulatory T Cells.Journal of personalized medicine · 2021Article
- The Signaling Pathway of PGEMediators of inflammation · 2021Review
- Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8Journal for immunotherapy of cancer · 2019Article
- Immune System Evasion as Hallmark of Melanoma Progression: The Role of Dendritic Cells.Frontiers in oncology · 2019Review
- Adenosine Receptors Influence Hypertension in Dahl Salt-Sensitive Rats: Dependence on Receptor Subtype, Salt Diet, and Sex.Hypertension (Dallas, Tex. : 1979) · 2018Article
- Article
- Augmentation of CAR T-cell Trafficking and Antitumor Efficacy by Blocking Protein Kinase A Localization.Cancer immunology research · 2016Article
- Purinergic regulation of the immune system.Nature reviews. Immunology · 2016Review
- Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection.Nature medicine · 2015Article
- Resistance of cyclooxygenase-2 expressing pancreatic ductal adenocarcinoma cells against γδ T cell cytotoxicity.Oncoimmunology · 2015Article
- Induced regulatory T cells in inhibitory microenvironments created by cancer.Expert opinion on biological therapy · 2014Review
- Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression?Cancer immunology, immunotherapy : CII · 2014Review
- Immune-suppressive properties of the tumor microenvironment.Cancer immunology, immunotherapy : CII · 2013Review
- Can the anti-inflammatory activities of β2-agonists be harnessed in the clinical setting?Drug design, development and therapy · 2013Review
- Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease.Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Previous studies document that PGE(2) and adenosine suppress production of inflammatory cytokines. The present study demonstrates for the first time that (1) PGE(2) and 2-chloroadenosine (CADO; a stable analog of adenosine) directly inhibit the cytolytic function of human tumor-infiltrating lymphocytes (TILs); (2) the combination PGE(2) and CADO have additive suppressive effects; and (3) the cooperative immunosuppressive actions of PGE(2) and CADO are mediated via EP2 receptors (EP2Rs) and A(2A) receptors (A(2A)Rs) and are due to amplification of cAMP production, activation of protein kinase A (PKA) and T cell receptor (TCR) inhibitor Csk leading to inhibition of Lck, ZAP-70 and Akt phosphorylation. (4) During ex vivo expansion, TILs undergo three stages of differentiation converting from TILs with high cytotoxic activity and relative resistance to combined EP2R/A(2A)R suppression (stage I) to TILs retaining high cytotoxicity and gaining sensitivity to combined suppression (stage II) and then to TILS that are less cytotoxic and very sensitive to combined suppression (stage III). (5) Finally, we find that pretreatment of TILs with non-inhibitory concentrations of EP2R agonists (such as PGE(2) or butaprost) or A(2A)R agonists (such as CADO or CGS21680) increases their cytotoxic activity and induces resistance to EP2R and A(2A)R inhibitory signaling (cross-resistance) due to homologous and heterologous desensitization and internalization of EP2Rs and A(2A)Rs, thus preventing their inhibitory signaling. We conclude that inducing resistance of TILs to the suppressive effects of PGE(2) and adenosine in the tumor microenvironment could represent a novel strategy for improving the efficacy of adoptive immunotherapy.
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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.