ArticleHaematologica2021
Targeting of the A2A adenosine receptor counteracts immunosuppression in vivo in a mouse model of chronic lymphocytic leukemia.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Potential oncogene VPS72 in hepatocellular carcinoma: prognostic and immune infiltration implications.European journal of medical research · 2026Article
- CAR Intrinsic Design Pre-Shapes Transcriptional and Metabolic Networks in CAR T Cells.Metabolites · 2026Article
- Review
- BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia.JCI insight · 2024Article
- The inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies.Acta pharmaceutica Sinica. B · 2024Review
- APurinergic signalling · 2023Article
- CRISPR-Cas9-Based Gene Knockout of Immune Checkpoints in Expanded NK Cells.International journal of molecular sciences · 2023Article
- The Immune Regulatory Role of Adenosine in the Tumor Microenvironment.International journal of molecular sciences · 2023Review
- Inhibitory effect of adenosine on adaptive antitumor immunity and intervention strategies.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Review
- Pharmacology of Adenosine Receptors: Recent Advancements.Biomolecules · 2023Review
- Lymphocytes from B-acute lymphoblastic leukemia patients present differential regulation of the adenosinergic axis depending on risk stratification.Discover oncology · 2022Article
- CD73 Promotes Chronic Lymphocytic Leukemia.Cancers · 2022Article
- Potentiating Cancer Immune TherapyFrontiers in cell and developmental biology · 2022Article
- Current Adenosinergic Therapies: What Do Cancer Cells Stand to Gain and Lose?International journal of molecular sciences · 2021Review
- T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective.Haematologica · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Tumor immunosuppression is a major cause for treatment failure and disease relapse, both in solid tumors and leukemia. Local hypoxia is among the conditions that cause immunosuppression, acting at least in part through the upregulation of extracellular adenosine levels, which potently suppress T cell responses and skew macrophages towards an M2 phenotype. Hence, there is intense investigation to identify drugs that target this axis. By using the TCL1 adoptive transfer CLL mouse model, we show that adenosine production and signaling are upregulated in the hypoxic lymphoid niches, where intense colonization of leukemic cells occurs. This leads to a progressive remodeling of the immune system towards tolerance, with expansion of T regulatory cells (Tregs), loss of CD8+ T cell cytotoxicity and differentiation of murine macrophages towards the patrolling (M2-like) subset. In vivo administration of SCH58261, an inhibitor the A2A adenosine receptor, re-awakens T cell responses, while limiting Tregs expansion, and re-polarizes monocytes towards the inflammatory (M1-like) phenotype. These results show for the first time the in vivo contribution of adenosine signaling to immune tolerance in CLL, and the translational implication of drugs interrupting this pathway. Although the effects of SCH58261 on leukemic cells are limited, interfering with adenosine signaling may represent an appealing strategy for combination-based therapeutic approaches.
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