ReviewCancer immunology research2014
Hostile, hypoxia-A2-adenosinergic tumor biology as the next barrier to overcome for tumor immunologists.
Review in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 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
133 citing papers in PubMed, 209 citations in OpenAlex.
- Clinical significance of CD73 in triple-negative breast cancer: multiplex analysis of a phase III clinical trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2018Trial
- CD39 on CD8European journal of immunology · 2026Review
- Ectonucleotidases CD39 and CD73 expression levels are independent and inverse predictors of survival in muscle-invasive bladder cancer.The journal of pathology. Clinical research · 2026Article
- Targeting conserved domains of hypoxia-inducible factors for cancer therapy.The Journal of experimental medicine · 2026Article
- Molecular mechanisms by which tumor cell CD73-mediated adenosine signaling drives M2 polarization of macrophages in non-small cell lung cancer.Frontiers in cell and developmental biology · 2026Article
- Modulating CD38 enzymatic activity during antibody-based immunotherapy in multiple myeloma: a basic science perspective.Frontiers in immunology · 2026Article
- Breaking hypoxic barrier: Oxygen-supplied nanomaterials for enhanced T cell-mediated tumor immunotherapy.International journal of pharmaceutics: X · 2025Review
- Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia.Purinergic signalling · 2025Review
- Targeting adenosine APurinergic signalling · 2025Review
- Tumor site-directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors.Nature communications · 2025Article
- Insights from Clinical Trials on AACS pharmacology & translational science · 2025Review
- Regulatory T cells converted from Th1 cells in tumors suppress cancer immunity via CD39.The Journal of experimental medicine · 2025Article
- Oxygen-carrying nanoemulsions and respiratory hyperoxia eliminate tumor hypoxia-induced immunosuppression.JCI insight · 2025Article
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- Enzymatic and microenvironmental regulation in adenosine metabolism-mediated immunosuppression.Frontiers in immunology · 2025Review
- Harnessing the power of tumor-draining lymph nodes: unveiling predictive biomarkers for immune checkpoint inhibitor.Exploration of targeted anti-tumor therapy · 2025Review
- CD73: a new immune checkpoint for leukemia treatment.Frontiers in immunology · 2025Review
- Adenosine A2AR in viral immune evasion and therapy: unveiling new avenues for treating COVID-19 and AIDS.Molecular biology reports · 2024Review
- Controlling Pericellular Oxygen Tension in Cell Culture Reveals Distinct Breast Cancer Responses to Low Oxygen Tensions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia-driven, A2A adenosine receptor (A2AR)-mediated (hypoxia-A2-adenosinergic), T-cell-autonomous immunosuppression was first recognized as critical and nonredundant in protecting normal tissues from inflammatory damage and autoimmunity. However, this immunosuppressive mechanism can be highjacked by bacteria and tumors to provide misguided protection for pathogens and cancerous tissues. Inhibitors of the hypoxia-A2-adenosinergic pathway represent a conceptually novel type of immunologic coadjuvants that could be combined with cancer vaccines, adoptive cell transfer, and/or blockade of negative immunologic regulators to further prolong patient survival and to minimize treatment-related side effects. In support of this approach are preclinical studies and findings that some human cancers are resistant to chemotherapies and immunotherapies due to the tumor-generated extracellular adenosine and A2AR on antitumor T and natural killer (NK) cells. Among the coadjuvants are (i) antagonists of A2AR, (ii) extracellular adenosine-degrading drugs, (iii) inhibitors of adenosine generation by CD39/CD73 ectoenzymes, and (iv) inhibitors of hypoxia-HIF-1α signaling. Combining these coadjuvants with CTLA-4 and/or PD-1 blockade is expected to have additive or even synergistic effects of targeting two different antitumor protective mechanisms. It is expected that even after multicombinatorial blockade of negative immunologic regulators, the antitumor T and NK cells would still be vulnerable to inhibition by hypoxia and A2AR. Yet to be tested is the potential capacity of coadjuvants to minimize the side effects of CTLA-4 and/or PD-1 blockade by decreasing the dose of blocking antibodies or by eliminating the need for dual blockade.
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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.