ArticleFrontiers in immunology2023
CAR and TCR form individual signaling synapses and do not cross-activate, however, can co-operate in T cell activation.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- High-Precision Intrinsic Interactome Elucidation of Chimeric Antigen Receptors via Photocatalytic Micromapping (μMap-CAR).Journal of the American Chemical Society · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma.Blood neoplasia · 2026Article
- Phosphoproteomic analysis of successive Jurkat CD19-CAR generations reveals TCRζ-driven signalling.Cellular signalling · 2026Article
- CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation.Science signaling · 2025Article
- CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization.Cell communication and signaling : CCS · 2025Review
- Discordant CAR-T cell signaling: implications of divergence from physiological T cell activation.Journal of translational medicine · 2025Review
- Safety and clinical efficacy of Relmacabtagene autoleucel (relma-cel) for systemic lupus erythematosus: a phase 1 open-label clinical trial.EClinicalMedicine · 2025Article
- Tailoring CAR surface density and dynamics to improve CAR-T cell therapy.Journal for immunotherapy of cancer · 2025Review
- CAR-mediated target recognition limits TCR-mediated target recognition of TCR- and CAR-dual-receptor-edited T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Vaccine-induced T cell receptor T cell therapy targeting a glioblastoma stemness antigen.Nature communications · 2025Article
- Effectors of the Future: Universal Chimeric Antigen Receptor.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- The immunobiology and therapeutic potential of regulatory T cells in autoimmune diseases and allergic diseases.Frontiers in immunology · 2025Review
- CAR-γδ T cells: a new paradigm of programmable innate immune sentinels and their systemic applications in cancer and beyond.Frontiers in immunology · 2025Review
- TMX1, a disulfide oxidoreductase, is necessary for T cell function through regulation of CD3ζ.bioRxiv : the preprint server for biology · 2024Article
- Arming Vδ2 T Cells with Chimeric Antigen Receptors to Combat Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells.Aging and disease · 2024Review
- Integration of ζ-deficient CARs into the CD3ζ gene conveys potent cytotoxicity in T and NK cells.Blood · 2024Article
- Endogenous Signaling Molecule Activating (ESMA) CARs: A Novel CAR Design Showing a Favorable Risk to Potency Ratio for the Treatment of Triple Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In engineered T cells the CAR is co-expressed along with the physiological TCR/CD3 complex, both utilizing the same downstream signaling machinery for T cell activation. It is unresolved whether CAR-mediated T cell activation depends on the presence of the TCR and whether CAR and TCR mutually cross-activate upon engaging their respective antigen. Here we demonstrate that the CD3ζ CAR level was independent of the TCR associated CD3ζ and could not replace CD3ζ to rescue the TCR complex in CD3ζ KO T cells. Upon activation, the CAR did not induce phosphorylation of TCR associated CD3ζ and, vice versa, TCR activation did not induce CAR CD3ζ phosphorylation. Consequently, CAR and TCR did not cross-signal to trigger T cell effector functions. On the membrane level, TCR and CAR formed separate synapses upon antigen engagement as revealed by total internal reflection fluorescence (TIRF) and fast AiryScan microscopy. Upon engaging their respective antigen, however, CAR and TCR could co-operate in triggering effector functions through combinatorial signaling allowing logic "AND" gating in target recognition. Data also imply that tonic TCR signaling can support CAR-mediated T cell activation emphasizing the potential relevance of the endogenous TCR for maintaining T cell capacities in the long-term.
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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.