ArticleScience signaling2019
Engineering γδT cells limits tonic signaling associated with chimeric antigen receptors.
Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 48 citations in OpenAlex.
- CAR signaling instructs divergent metabolic reprogramming and functional fates in αβ and γδ T cells.Cellular & molecular immunology · 2026Article
- Harnessing the potential of γδ T cells through engineering and combination treatment for cancer therapies.Nature communications · 2026Review
- Analysis of the tumor reactivity of autologous TILs and allogeneic γδ T cells via tumor organoid-immune cell coculture.Journal of translational medicine · 2026Article
- Re-Tooling of γδ T Cells for Cancer Immunotherapy Using Advanced Manufacturing and Genetic Engineering.Cells · 2026Review
- Beyond αβ T cells: unlocking the potential of diverse immune cells in CAR modification.Clinical science (London, England : 1979) · 2026Review
- CAR-T cell therapy in glioblastoma: from αβ to γδ T-cell platforms.Oncology reviews · 2026Review
- Phenoscaping Reveals Multimodal γδ T-cell Cytotoxicity as a Strategy to Overcome Cancer Cell-Mediated Immunomodulation.Cancer research · 2025Article
- Disrupting the balance between activating and inhibitory receptors of γδT cells for effective cancer immunotherapy.Nature reviews. Cancer · 2025Review
- CyTOF as a suitable tool for stratification and monitoring of cancer patients.Journal of translational medicine · 2025Review
- Engineering innate immune cells for cancer immunotherapy.Nature biotechnology · 2025Review
- The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.Experimental hematology & oncology · 2024Review
- Cancer immunotherapy by γδ T cells.Science (New York, N.Y.) · 2024Review
- Review
- Challenges and strategies in relation to effective CAR-T cell immunotherapy for solid tumors.Medical oncology (Northwood, London, England) · 2024Review
- Advancements in γδT cell engineering: paving the way for enhanced cancer immunotherapy.Frontiers in immunology · 2024Review
- CAR products from novel sources: a new avenue for the breakthrough in cancer immunotherapy.Frontiers in immunology · 2024Review
- GD2-targeting therapy: a comparative analysis of approaches and promising directions.Frontiers in immunology · 2024Review
- Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023Review
- Single-Cell Analysis in Immuno-Oncology.International journal of molecular sciences · 2023Review
- New cell sources for CAR-based immunotherapy.Biomarker research · 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
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Despite the benefits of chimeric antigen receptor (CAR)-T cell therapies against lymphoid malignancies, responses in solid tumors have been more limited and off-target toxicities have been more marked. Among the possible design limitations of CAR-T cells for cancer are unwanted tonic (antigen-independent) signaling and off-target activation. Efforts to overcome these hurdles have been blunted by a lack of mechanistic understanding. Here, we showed that single-cell analysis with time course mass cytometry provided a rapid means of assessing CAR-T cell activation. We compared signal transduction in expanded T cells to that in T cells transduced to express second-generation CARs and found that cell expansion enhanced the response to stimulation. However, expansion also induced tonic signaling and reduced network plasticity, which were associated with expression of the T cell exhaustion markers PD-1 and TIM-3. Because this was most evident in pathways downstream of CD3ζ, we performed similar analyses on γδT cells that expressed chimeric costimulatory receptors (CCRs) lacking CD3ζ but containing DAP10 stimulatory domains. These CCR-γδT cells did not exhibit tonic signaling but were efficiently activated and mounted cytotoxic responses in the presence of CCR-specific stimuli or cognate leukemic cells. Single-cell signaling analysis enabled detailed characterization of CAR-T and CCR-T cell activation to better understand their functional activities. Furthermore, we demonstrated that CCR-γδT cells may offer the potential to avoid on-target, off-tumor toxicity and allo-reactivity in the context of myeloid malignancies.
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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.