ArticleCancer research2013
Enhanced effector responses in activated CD8+ T cells deficient in diacylglycerol kinases.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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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.
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Who cites it
76 citing papers in PubMed, 120 citations in OpenAlex.
- Article
- Generation of therapeutic T cells from human induced pluripotent stem cells.Inflammation and regeneration · 2026Review
- CRISPR-screen informed engineered T cell therapies.Frontiers in immunology · 2026Review
- Stereoselective Degradation of Diacylglycerol Kinases Potentiate T cell Activation and Tumor Cell Cytotoxicity.bioRxiv : the preprint server for biology · 2025Article
- Accelerating CAR-T Cell Therapies with Small-Molecule Inhibitors.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- DGKα/ζ inhibition lowers the TCR affinity threshold and potentiates antitumor immunity.Science advances · 2023Article
- Predicting small molecule binding pockets on diacylglycerol kinases using chemoproteomics and AlphaFold.RSC chemical biology · 2023Article
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy.Cell reports. Medicine · 2023Article
- Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells.Nature biomedical engineering · 2023Article
- Innate immune response restarts adaptive immune response in tumors.Frontiers in immunology · 2023Review
- The protective role of the microenvironment in hairy cell leukemia treatment: Facts and perspectives.Frontiers in oncology · 2023Review
- CAR T Cells: Cancer Cell Surface Receptors Are the Target for Cancer Therapy.Advanced pharmaceutical bulletin · 2022Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Combination therapy for hepatocellular carcinoma with diacylglycerol kinase alpha inhibition and anti-programmed cell death-1 ligand blockade.Cancer immunology, immunotherapy : CII · 2022Article
- Delivering Glioblastoma a Kick-DGKα Inhibition as a Promising Therapeutic Strategy for GBM.Cancers · 2022Review
- Enhanced Chimeric Antigen Receptor T Cell Therapy through Co-Application of Synergistic Combination Partners.Biomedicines · 2022Review
- CAR-T Therapy for Pediatric High-Grade Gliomas: Peculiarities, Current Investigations and Future Strategies.Frontiers in immunology · 2022Review
- Cellular networks controlling T cell persistence in adoptive cell therapy.Nature reviews. Immunology · 2021Review
- Diacylglycerol kinase α inhibition cooperates with PD-1-targeted therapies to restore the T cell activation program.Cancer immunology, immunotherapy : CII · 2021Article
16 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
Recent clinical trials have shown promise in the use of chimeric antigen receptor (CAR)-transduced T cells; however, augmentation of their activity may broaden their clinical use and improve their efficacy. We hypothesized that because CAR action requires proteins essential for T-cell receptor (TCR) signal transduction, deletion of negative regulators of these signaling pathways would enhance CAR signaling and effector T-cell function. We tested CAR activity and function in T cells that lacked one or both isoforms of diacylglycerol kinase (dgk) expressed highly in T cells, dgkα and dgkζ, enzymes that metabolize the second messenger diacylglycerol (DAG) and limit Ras/ERK activation. We found that primary murine T cells transduced with CARs specific for the human tumor antigen mesothelin showed greatly enhanced cytokine production and cytotoxicity when cocultured with a murine mesothelioma line that stably expresses mesothelin. In addition, we found that dgk-deficient CAR-transduced T cells were more effective in limiting the growth of implanted tumors, both concurrent with and after establishment of tumor. Consistent with our studies in mice, pharmacologic inhibition of dgks also augments function of primary human T cells transduced with CARs. These results suggest that deletion of negative regulators of TCR signaling enhances the activity and function of CAR-expressing T cells and identify dgks as potential targets for improving the clinical potential of CARs.
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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.