ArticleThe Journal of clinical investigation2017
Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04969315 (Phase I/II First-in-Human Study of TT-10), which is not on this map. Cited by 194 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Phase I/II First-in-Human Study of TT-10 (PORT-6), an Adenosine 2A Receptor Antagonist, and PORT-7, an Adenosine 2B Receptor Antagonist, as Single Agents and in Combination in Participants With Advanced Selected Solid Tumors
Who cites it
194 citing papers in PubMed, 310 citations in OpenAlex.
- Cancer associated fibroblast-T cell crosstalk promotes purinergic synthesis in non-small cell lung cancer (NSCLC).Oncoimmunology · 2026Article
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- CDK4/6 inhibition enhances CAR-T cell therapy in solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- 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
- Immune Evasion in Ovarian Cancer Peritoneal Metastasis: Mechanisms and Biomarker-Guided Therapeutic Matching.Journal of cellular physiology · 2026Review
- Review
- Tumor cell death by ferroptosis contributes to an immunosuppressive tumor microenvironment in syngeneic murine models of cancer.Cancer & metabolism · 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
- Organoid models: reshaping the paradigm for precision development and evaluation of CAR-T cell therapies.Frontiers in bioengineering and biotechnology · 2026Review
- Targeting solid tumors with TCR-T cells: mechanisms, progress, and challenges.Frontiers in oncology · 2026Review
- Enhancing Immunotherapy in Diffuse Large B-Cell Lymphoma: The Synergistic Potential of Metabolic Checkpoint Inhibitors and Immunomodulation.OncoTargets and therapy · 2026Review
- Targeting the Dynamics Between TAMs and CAR-T Cells in Solid Tumor Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Spatial Treg niches and the therapeutic reprogramming of tumour tolerance in cancer.Frontiers in cell and developmental biology · 2026Review
- Improving CAR T cell therapy against malignancies through gene knock-down/out strategies: a systematic review.Cancer cell international · 2025Review
- 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
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer 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
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Engineering CAR-T cells for solid tumors: bispecific antigen targeting, tumor microenvironment modulation, and toxicity control.Immunologic research · 2025Review
134 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
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and chronic lymphoblastic leukemia. However, treatment of solid tumors using CAR T cells has been largely unsuccessful to date, partly because of tumor-induced immunosuppressive mechanisms, including adenosine production. Previous studies have shown that adenosine generated by tumor cells potently inhibits endogenous antitumor T cell responses through activation of adenosine 2A receptors (A2ARs). Herein, we have observed that CAR activation resulted in increased A2AR expression and suppression of both murine and human CAR T cells. This was reversible using either A2AR antagonists or genetic targeting of A2AR using shRNA. In 2 syngeneic HER2+ self-antigen tumor models, we found that either genetic or pharmacological targeting of the A2AR profoundly increased CAR T cell efficacy, particularly when combined with PD-1 blockade. Mechanistically, this was associated with increased cytokine production of CD8+ CAR T cells and increased activation of both CD8+ and CD4+ CAR T cells. Given the known clinical relevance of the CD73/adenosine pathway in several solid tumor types, and the initiation of phase I trials for A2AR antagonists in oncology, this approach has high translational potential to enhance CAR T cell efficacy in several cancer types.
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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.