ArticleCell2021
An NK-like CAR T cell transition in CAR T cell dysfunction.
Open access · greenAbstract read
In one paragraph
Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 272 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
272citing papers in PubMed, 1 pooled it
24.8field-weighted citation impact, top 1% of its field
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
272 citing papers in PubMed, 1 synthesis or guideline pooled it, 383 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- A phase I/II trial of WT1-specific TCR gene therapy for patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation: skewing towards NK-like phenotype impairs T cell function and persistence.Nature communications · 2025Trial
- Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion.Nature communications · 2024Trial
- BCMA-BBZ-OX40 CAR-T Therapy Using an Instant Manufacturing Platform in Multiple Myeloma.Journal for immunotherapy of cancer · 2024Trial
- Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.The Journal of clinical investigation · 2024Trial
- Article
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Augmenting CAR T cell functionality and metabolism through CD39 downtuning.Molecular therapy. Oncology · 2026Article
- Scalable generation of hematopoietic stem cell-engineered off-the-shelf mono-specific cytotoxic T cells targeting solid tumors.Cell reports. Medicine · 2026Article
- Programmable CAR-engaging particles rewire human CAR T-cell signaling for sustainable ex vivo expansion.Nature communications · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Epigenetic insights and innovations for overcoming barriers in CAR-T cell therapy for cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The CREM-IL-15 axis: decoding the persistence-exhaustion paradox in NK cell immunotherapy.Cancer immunology, immunotherapy : CII · 2026Review
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- Single-nucleus transcriptomic atlas of postnatal camel liver development identifies candidate adaptive features.BMC genomics · 2026Article
- Anti-CAR Immunity Drives Acquired Therapeutic Resistance to GD2-CAR T Cell Therapy in Diffuse Midline Glioma.medRxiv : the preprint server for health sciences · 2026Article
- αvβ3 CAR-T Cells Simultaneously Targeting Tumor and Metastases Produce Highly Effective Control in Preclinical Models of Melanoma and Triple-Negative Breast Cancer.Molecular cancer therapeutics · 2026Article
- A guide to CAR T cell therapies: development, current status and future prospects.Nature reviews. Immunology · 2026Review
- EZH2 and intracellular CaCellular & molecular immunology · 2026Article
212 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors at 5 institutions in 1 country.
Charly R GoodDepartment of Cell and Developmental Biology, Penn Institute of Epigenetics, Perelman School of Medicine, Philadelphia, PA 19104, USA.
M Angela AznarCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Shunichiro KuramitsuCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Parisa SamarehDepartment of Cell and Developmental Biology, Penn Institute of Epigenetics, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Sangya AgarwalCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Greg DonahueDepartment of Cell and Developmental Biology, Penn Institute of Epigenetics, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Kenichi IshiyamaDepartment of Microbiology and Immunology, University of California San Francisco and the Parker Institute for Cancer Immunotherapy at the University of California San Francisco, San Francisco, California 94143, USA.
Nils WellhausenCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Austin K RennelsCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Yujie MaCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Lifeng TianCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA 19104, USA.
Sonia GuedanCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Katherine A AlexanderDepartment of Cell and Developmental Biology, Penn Institute of Epigenetics, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Zhen ZhangDepartment of Cell and Developmental Biology, Penn Institute of Epigenetics, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Philipp C RommelCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Nathan SinghCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Karl M GlastadDepartment of Cell and Developmental Biology, Penn Institute of Epigenetics, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Max W RichardsonDepartment of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
Keisuke WatanabeCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Janos L TanyiAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mark H O'HaraAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
Marco RuellaCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
Simon F LaceyCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA 19104, USA.
Edmund K MoonCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Stephen J SchusterLymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
Steven M AlbeldaCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Lewis L LanierDepartment of Microbiology and Immunology, University of California San Francisco and the Parker Institute for Cancer Immunotherapy at the University of California San Francisco, San Francisco, California 94143, USA.
Regina M YoungCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: ryoung@upenn.edu.
Shelley L BergerDepartment of Cell and Developmental Biology, Penn Institute of Epigenetics, Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: bergers@pennmedicine.upenn.edu.
Carl H JuneCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: cjune@upenn.edu.
University of Pennsylvania · USParker Institute for Cancer Immunotherapy · USUniversity of California, San Francisco · USPenn Center for AIDS Research · USUPMC Hillman Cancer Center · US
Funding
Project 3: Combinatorial and gene-editing approaches to enhance the efficacy of CAR T cell therapy of multiple myeloma.P01CA214278 · NCI · UNIVERSITY OF PENNSYLVANIA · PI CARL H. JUNE · 2017 to 2026
$26.8MResearch BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MProject 3 - Immune analysis of clinical trial samplesP01CA217805 · NCI · UNIVERSITY OF PENNSYLVANIA · PI HWANG, WEI-TING · 2018 to 2022
$10.4MRole of PCAF/GCN5 Acetylation on p53 TransactivationR01CA078831 · NCI · WISTAR INSTITUTE · PI BERGER, SHELLEY L · 1999 to 2022
$7.8MResistance To Targeted Immunotherapies:CART19 as a ParadigmR00CA212302 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUELLA, MARCO · 2018 to 2020
$608kUCSF DVS CyTOF Mass CytometerS10OD018040 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LANIER, LEWIS LEE · 2014 to 2014
$600kResistance To Targeted Immunotherapies:CART19 as a ParadigmK99CA212302 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUELLA, MARCO · 2017 to 2018
$348kNovel Roles of p53 Post Translational Modifications in CancerF32CA232466 · NCI · UNIVERSITY OF PENNSYLVANIA · PI GOOD, CHARLY RYAN · 2019 to 2019
$53kNCI NIH HHS F32 CA232466NCI NIH HHS K99 CA212302NCI NIH HHS P01 CA214278NCI NIH HHS P01 CA217805NCI NIH HHS R00 CA212302NCI NIH HHS R01 CA078831NCI NIH HHS T32 CA009140NIDDK NIH HHS P30 DK063720NIH HHS S10 OD018040
Abstract
Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematological malignancies but remains ineffective in solid tumors, due in part to CAR T cell exhaustion in the solid tumor microenvironment. To study dysfunction of mesothelin-redirected CAR T cells in pancreatic cancer, we establish a robust model of continuous antigen exposure that recapitulates hallmark features of T cell exhaustion and discover, both in vitro and in CAR T cell patients, that CAR dysregulation is associated with a CD8+ T-to-NK-like T cell transition. Furthermore, we identify a gene signature defining CAR and TCR dysregulation and transcription factors, including SOX4 and ID3 as key regulators of CAR T cell exhaustion. Our findings shed light on the plasticity of human CAR T cells and demonstrate that genetic downmodulation of ID3 and SOX4 expression can improve the efficacy of CAR T cell therapy in solid tumors by preventing or delaying CAR T cell dysfunction.
Indexed as
AnimalsCD8-Positive T-LymphocytesCell Line, TumorHEK293 CellsHumansImmunotherapy, AdoptiveInhibitor of Differentiation ProteinsMaleMiceMice, KnockoutMice, NudeMice, SCIDNeoplasm ProteinsPancreatic NeoplasmsReceptors, Chimeric AntigenSOXC Transcription FactorsID3 protein, humanInhibitor of Differentiation ProteinsNeoplasm ProteinsReceptors, Chimeric AntigenSOX4 protein, humanSOXC Transcription FactorscancerCAR T cellcell transfer therapyID3immunologyimmunotherapyNK-like T cellpancreatic cancersingle-cell RNA-seqSOX4T cell dysfunctionT cell exhaustion
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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.