ArticleJournal for immunotherapy of cancer2021
Designed improvement to T-cell immunotherapy by multidimensional single cell profiling.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Mapping T cell dynamics to molecular profiles through behavior-guided transcriptomics.Nature protocols · 2025Review
- Heterogeneity of T cells regulates tumor immunity mediated by Helicobacter pylori infection in gastric cancer.BMC cancer · 2025Article
- The Efficiency of Brain-Derived Neurotrophic Factor Secretion by mRNA-Electroporated Regulatory T Cells Is Highly Impacted by Their Activation Status.European journal of immunology · 2025Article
- A thermoplastic chip for 2D and 3D correlative assays combining screening and high-resolution imaging of immune cell responses.Cell reports methods · 2025Article
- Cellular behavior analysis from live-cell imaging of TCR T cell-cancer cell interactions.bioRxiv : the preprint server for biology · 2024Article
- CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis.Cancer discovery · 2024Article
- Identification of a clinically efficacious CAR T cell subset in diffuse large B cell lymphoma by dynamic multidimensional single-cell profiling.Nature cancer · 2024Article
- BEHAV3D: a 3D live imaging platform for comprehensive analysis of engineered T cell behavior and tumor response.Nature protocols · 2024Article
- Decoding the mechanisms of chimeric antigen receptor (CAR) T cell-mediated killing of tumors: insights from granzyme and Fas inhibition.Cell death & disease · 2024Article
- Current advances in experimental and computational approaches to enhance CAR T cell manufacturing protocols and improve clinical efficacy.Frontiers in molecular medicine · 2024Review
- Bridging live-cell imaging and next-generation cancer treatment.Nature reviews. Cancer · 2023Review
- Transcriptomic Approaches in Studies on and Applications of Chimeric Antigen Receptor T Cells.Biomedicines · 2023Review
- Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses.The Journal of clinical investigation · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAdoptive cell therapy based on the infusion of chimeric antigen receptor (CAR) T cells has shown remarkable efficacy for the treatment of hematologic malignancies. The primary mechanism of action of these infused T cells is the direct killing of tumor cells expressing the cognate antigen. However, understanding why only some T cells are capable of killing, and identifying mechanisms that can improve killing has remained elusive.
methodsTo identify molecular and cellular mechanisms that can improve T-cell killing, we utilized integrated high-throughput single-cell functional profiling by microscopy, followed by robotic retrieval and transcriptional profiling.
resultsWith the aid of mathematical modeling we demonstrate that non-killer CAR T cells comprise a heterogeneous population that arise from failure in each of the discrete steps leading to the killing. Differential transcriptional single-cell profiling of killers and non-killers identified CD137 as an inducible costimulatory molecule upregulated on killer T cells. Our single-cell profiling results directly demonstrate that inducible CD137 is feature of killer (and serial killer) T cells and this marks a different subset compared with the CD107a
conclusionsBroadly, our results illustrate that while non-killer T cells are reflective of population heterogeneity, integrated single-cell profiling can enable identification of mechanisms that can enhance the function/proliferation of killer T cells leading to direct anti-tumor benefit.
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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.