ArticleCancer research2014
Adenosine A2A receptors intrinsically regulate CD8+ T cells in the tumor microenvironment.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 177 citations in OpenAlex.
- Suppressive effects of deep balanced anesthesia on cellular immunity and protein expression: a randomized-controlled pilot study.BMC anesthesiology · 2025Trial
- Contrasting functions of CD73 and adenosine in CD8+ T-cell exhaustion during antitumor immunity.Oncoimmunology · 2026Article
- Purinergic activity of circulating extracellular vesicles associates with disease progression in melanoma.Oncoimmunology · 2026Article
- Tumor cell death by ferroptosis contributes to an immunosuppressive tumor microenvironment in syngeneic murine models of cancer.Cancer & metabolism · 2026Article
- Integrative machine learning models reveal immune and metabolic signatures predictive of colorectal cancer prognosis.Discover oncology · 2026Article
- Tumor cell death by ferroptosis contributes to an immunosuppressive tumor microenvironment in syngeneic murine models of cancer.bioRxiv : the preprint server for biology · 2026Article
- T cell-macrophage crosstalk in GVHD and cancer immunotherapy.Cell investigation · 2025Article
- Advances in integrating biomaterials with CAR-T cells for enhancing solid tumor therapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- CAA-derived IL-6 promoted the PD-L1 expression of breast cancer via STAT3/miR-497a-5p signaling.Journal of cancer research and clinical oncology · 2025Article
- 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
- Regulatory T cells converted from Th1 cells in tumors suppress cancer immunity via CD39.The Journal of experimental medicine · 2025Article
- Dendritic cell maturation in cancer.Nature reviews. Cancer · 2025Review
- Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.Frontiers in immunology · 2025Review
- GPCRs: emerging targets for novel T cell immune checkpoint therapy.Cancer immunology, immunotherapy : CII · 2024Review
- CD39 Is Expressed on Functional Effector and Tissue-resident Memory CD8+ T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Extracellular vesicles from seminal plasma interact with T cells in vitro and drive their differentiation into regulatory T-cells.Journal of extracellular vesicles · 2024Article
- GRHL2 suppression of NT5E/CD73 in breast cancer cells modulates CD73-mediated adenosine production and T cell recruitment.iScience · 2024Article
- Critical role of the gut microbiota in immune responses and cancer immunotherapy.Journal of hematology & oncology · 2024Review
- The landscape of cancer-rewired GPCR signaling axes.Cell genomics · 2024Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Adenosine A(2A) receptor (A(2A)R) blockade enhances innate and adaptive immune responses. However, mouse genetic studies have shown that A(2A)R deletion does not inhibit the growth of all tumor types. In the current study, we showed that growth rates for ectopic melanoma and bladder tumors are increased in Adora2a(-/-) mice within 2 weeks of tumor inoculation. A(2A)R deletion in the host reduced numbers of CD8(+) T cells and effector-memory differentiation of all T cells. To examine intrinsic functions in T cells, we generated mice harboring a T-cell-specific deletion of A(2A)R. In this host strain, tumor-bearing mice displayed increased growth of ectopic melanomas, decreased numbers of tumor-associated T cells, reduced effector-memory differentiation, and reduced antiapoptotic IL7Rα (CD127) expression on antigen-experienced cells. Intratumoral pharmacologic blockade similarly reduced CD8(+) T-cell density within tumors in wild-type hosts. We found that A(2A)R-proficient CD8(+) T cells specific for melanoma cells displayed a relative survival advantage in tumors. Thus, abrogating A(2A)R signaling appeared to reduce IL7R expression, survival, and differentiation of T cells in the tumor microenvironment. One implication of these results is that the antitumor effects of A(2A)R blockade that can be mediated by activation of cytotoxic T cells may be overcome in some tumor microenvironments as a result of impaired T-cell maintenance and effector-memory differentiation. Thus, our findings imply that the efficacious application of A(2A)R inhibitors for cancer immunotherapy may require careful dose optimization to prevent activation-induced T-cell death in tumors.
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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.