ArticleCancer immunology research2022
Adenosine A2a Receptor Antagonism Restores Additive Cytotoxicity by Cytotoxic T Cells in Metabolically Perturbed Tumors.
Article in Cancer immunology research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- T-Cell Exhaustion in the Tumor Microenvironment: Subcellular Dysfunction, Pan-Cancer Characteristics, and Therapeutic Interventions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Glycocalyx micro- and nanodomains in cell-cell and cell-matrix interactions revealed by enhanced click chemistry.Nature communications · 2026Article
- Adenosine signaling in tumor immune escape: metabolic checkpoints, myeloid suppression, and combination immunotherapy.Frontiers in oncology · 2026Review
- The CD73-adenosine axis in melanoma: from multidimensional regulation to precision immunotherapy.Frontiers in immunology · 2026Review
- Metabolic reprogramming networks in the gastric cancer tumor microenvironment: an integrated axis of nutrient competition, metabolic crosstalk, and immunosuppression.Frontiers in immunology · 2026Review
- Single-Cell Transcriptomics Reveals Biomarkers for NK Cell Dysfunction in Endometriosis-Associated Immune Dysregulation.Mediators of inflammation · 2026Article
- Neoantigen mRNA vaccines and AHuman vaccines & immunotherapeutics · 2025Review
- Half-Pipe Melt Electrowritten Scaffolds Support Engineering of an Immunocompetent Hydrogel-Embedded Intestine-on-a-Chip.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.Frontiers in immunology · 2025Review
- Ameliorated cellular hallmarks of myotonic dystrophy in hybrid myotubes from patient and unaffected donor cells.Stem cell research & therapy · 2024Article
- Review
- Tumor derived exosomal ENTPD2 impair CD8Cell communication and signaling : CCS · 2024Article
- Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.Cell reports. Medicine · 2024Article
- Unlocking the potential of T-cell metabolism reprogramming: Advancing single-cell approaches for precision immunotherapy in tumour immunity.Clinical and translational medicine · 2024Review
- Current perspectives and trends of CD39-CD73-eAdo/A2aR research in tumor microenvironment: a bibliometric analysis.Frontiers in immunology · 2024Article
- Pharmacology of Adenosine Receptors: Recent Advancements.Biomolecules · 2023Review
- Review
- Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors.Biology · 2023Review
- Volume imaging to interrogate cancer cell-tumor microenvironment interactions in space and time.Frontiers in immunology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Cytotoxic T lymphocytes (CTL) are antigen-specific effector cells with the ability to eradicate cancer cells in a contact-dependent manner. Metabolic perturbation compromises the CTL effector response in tumor subregions, resulting in failed cancer cell elimination despite the infiltration of tumor-specific CTLs. Restoring the functionality of these tumor-infiltrating CTLs is key to improve immunotherapy. Extracellular adenosine is an immunosuppressive metabolite produced within the tumor microenvironment. Here, by applying single-cell reporter strategies in 3D collagen cocultures in vitro and progressing tumors in vivo, we show that adenosine weakens one-to-one pairing of activated effector CTLs with target cells, thereby dampening serial cytotoxic hit delivery and cumulative death induction. Adenosine also severely compromised CTL effector restimulation and expansion. Antagonization of adenosine A2a receptor (ADORA2a) signaling stabilized and prolonged CTL-target cell conjugation and accelerated lethal hit delivery by both individual contacts and CTL swarms. Because adenosine signaling is a near-constitutive confounding parameter in metabolically perturbed tumors, ADORA2a targeting represents an orthogonal adjuvant strategy to enhance immunotherapy efficacy.
Indexed as
Identifiers
What OpenQuestion holds
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.