ArticleCancer immunology, immunotherapy : CII2018
Inhibition of the adenosine A2a receptor modulates expression of T cell coinhibitory receptors and improves effector function for enhanced checkpoint blockade and ACT in murine cancer models.
Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.
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Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 180 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- EBV hijacks the metabolic function of CD73 to resist the antitumor function of NK cells.NPJ precision oncology · 2026Article
- Immune checkpoint crosstalk between LAG-3 and CD39/CD73 in glioblastoma: dual-pathway regulation of metabolic exhaustion and therapeutic reversal strategies.Journal of the Egyptian National Cancer Institute · 2026Review
- Immunosuppressive Pathways in Cutaneous Melanoma: Functional Integration Between PD-1 and CD73 and Therapeutic Implications.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The ATP-adenosine axis as a driver of tumor-associated macrophage reprogramming in colorectal cancer: mechanistic insights into immune evasion and therapeutic vulnerabilities.Purinergic signalling · 2026Review
- Integrated metabolomics and transcriptomics analysis unveils key metabolic pathways and potential biomarkers in clear cell renal cell carcinoma.Discover oncology · 2026Article
- <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>.Oncology reports · 2026Review
- Semaphorin 6D drives anti-tumor type I interferon responses to reprogram the tumor microenvironment in colorectal cancer.Cell death & disease · 2026Article
- Potassium channels as an ionic checkpoint in tumor immunity.Frontiers in pharmacology · 2026Review
- Understanding the Tumor Microenvironmental Mechanisms Driving Immunotherapy Resistance in Colorectal Cancer Liver Metastases.Oncology research · 2026Review
- CD73 expression as a resistance mechanism in advancedFrontiers in oncology · 2026Article
- The CD73-adenosine axis in melanoma: from multidimensional regulation to precision immunotherapy.Frontiers in immunology · 2026Review
- IFNβ-pSTAT1-IRF1 axis controls colorectal tumor development through induction of immunogenic Ly6CNeoplasia (New York, N.Y.) · 2026Article
- CRISPR/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies.Current gene therapy · 2026Review
- Tumor-associated macrophages: untapped molecular targets to improve T cell-based immunotherapy.Molecular cancer · 2025Review
- Mechanisms of T-cell metabolic reprogramming in the microenvironment of acute myeloid leukemia and its therapeutic potential (Review).Oncology letters · 2025Review
- The glioma microenvironment and its impact on antitumor immunity.Neuro-oncology advances · 2025Review
- Purinergic pathways and their clinical use in the treatment of acute myeloid leukemia.Purinergic signalling · 2025Review
- Non-Canonical Functions of Adenosine Receptors: Emerging Roles in Metabolism, Immunometabolism, and Epigenetic Regulation.International journal of molecular sciences · 2025Review
- Tumor site-directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors.Nature communications · 2025Article
68 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
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenosine signaling via the A2a receptor (A2aR) is emerging as an important checkpoint of immune responses. The presence of adenosine in the inflammatory milieu or generated by the CD39/CD73 axis on tissues or T regulatory cells serves to regulate immune responses. By nature of the specialized metabolism of cancer cells, adenosine levels are increased in the tumor microenvironment and contribute to tumor immune evasion. To this end, small molecule inhibitors of the A2aR are being pursued clinically to enhance immunotherapy. Herein, we demonstrate the ability of the novel A2aR antagonist, CPI-444, to dramatically enhance immunologic responses in models of checkpoint therapy and ACT in cancer. Furthermore, we demonstrate that A2aR blockade with CPI-444 decreases expression of multiple checkpoint pathways, including PD-1 and LAG-3, on both CD8+ effector T cells (Teff) and FoxP3+ CD4+ regulatory T cells (Tregs). Interestingly, our studies demonstrate that A2aR blockade likely has its most profound effects during Teff cell activation, significantly decreasing PD-1 and LAG-3 expression at the draining lymph nodes of tumor bearing mice. In contrast to previous reports using A2aR knockout models, pharmacologic blockade with CPI-444 did not impede CD8 T cell persistence or memory recall. Overall these findings not only redefine our understanding of the mechanisms by which adenosine inhibits immunity but also have important implications for the design of novel immunotherapy regimens.
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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.