ArticleNature cancer2024
Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome.
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Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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31citing papers in PubMed, 1 pooled it
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A systematic review and meta-analysis of shRNA-IL-6-engineered CAR-T cells for B-cell acute lymphoblastic leukemia: a stepping stone toward risk-free immunotherapy.Bioscience reports · 2026Pooled it
- Anti-inflammatory approaches in cancer immunotherapy-induced autoimmunity.EULAR rheumatology open · 2026Review
- Identifying a Csmd3Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- A transcriptomic microglia taxonomy across mouse and human pathologies.Nature immunology · 2026Article
- The promise of immunotherapy for central nervous system tumours.Nature reviews. Immunology · 2026Review
- Diurnal rhythm in chimeric antigen receptor T cell effectiveness in an observational study of 715 patients.JCI insight · 2026Observational
- De novo H3.3K27M-altered diffuse midline glioma in human brainstem organoids to dissect GD2 CAR T cell function.Nature cancer · 2026Article
- Neurotoxicity of Immunotherapy: Immune Checkpoint Inhibitor-Related Encephalitis vs. Immune Effector Cell-Associated Neurotoxicity Syndrome.World journal of oncology · 2026Review
- Chimeric antigen receptor T-cell therapy in neuroimmune diseases: mechanistic rationale, clinical experience, and translational challenges.Frontiers in immunology · 2026Review
- CAR-T Therapy Can Be a Useful Treatment Modality for More Than Just Hematologic Malignancies.Internal medicine (Tokyo, Japan) · 2026Review
- Repurposing mitochondrial-targeting drugs for management of ICANS in CAR T-cell therapy: a novel steroid-sparing approach.Frontiers in pharmacology · 2026Article
- Mechanisms and treatment of cancer therapy-induced peripheral and central neurotoxicity.Nature reviews. Cancer · 2025Review
- Identifying Biomedical Entities for Datasets in Scientific Articles: 4-Step Cache-Augmented Generation Approach Using GPT-4o and PubTator 3.0.JMIR formative research · 2025Article
- AIstain: Enhancing microglial phagocytosis analysis through deep learning.Cell reports methods · 2025Article
- Neurotoxicity in central nervous system tumors treated with CAR T cell therapy: a review.Journal of neuro-oncology · 2025Review
- Barriers and solutions for CAR-T therapy in solid tumors.Cancer gene therapy · 2025Review
- Neurological complications of CAR T cell therapy for cancers.Nature reviews. Neurology · 2025Review
- Immune checkpoint inhibition perturbs neuro-immune homeostasis and impairs cognitive function.Journal of experimental & clinical cancer research : CR · 2025Article
- PET-based immunomapping of intratumoral CD4Science advances · 2025Article
Corrections and comments
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Authors and funding
64 authors.
Janaki Manoja VinnakotaDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Francesca BiavascoDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Marius SchwabenlandInstitute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-2205-5427
Chintan ChhatbarInstitute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Rachael C AdamsDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Daniel ErnyInstitute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0001-6000-8838
Sandra DuquesneDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Nadia El KhawankyDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Dominik SchmidtDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-7744-1248
Viktor FetschDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Alexander ZähringerDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Henrike SaliéDepartment of Medicine II, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-2993-3782
Dimitrios AthanassopoulosDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Lukas M BraunDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-0770-4994
Nora R JavorniczkyDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Jenny N H G HoDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Katrin KierdorfInstitute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-9272-4780
Reinhard MarksDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Ralph WäschDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0813-3444
Federico SimonettaDivision of Hematology, Geneva University Hospitals Geneva, Geneva, Switzerland.
Geoffroy AndrieuxInstitute of Medical Bioinformatics and Systems Medicine, Medical Center, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-5389-9481
Dietmar PfeiferDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Gianni MonacoInstitute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Christian CapitiniPediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2276-6731
Terry J FryCenter for Cancer and Blood Disorders, Children's Hospital Colorado and Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0001-8044-5226
Thomas BlankInstitute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-3969-405X
Bruce R BlazarMasonic Cancer Center and Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular Therapy, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-9608-9841
Eva WagnerDepartment of Hematology and Medical Oncology, Johannes Gutenberg-University Medical Center, Mainz, Germany.ORCID http://orcid.org/0000-0002-0728-2253
Matthias TheobaldDepartment of Hematology and Medical Oncology, Johannes Gutenberg-University Medical Center, Mainz, Germany.
Clemens SommerInstitute of Neuropathology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Matthias StelljesDepartment of Medicine/Hematology and Oncology, University of Münster, Münster, Germany.
Christian ReichertsDepartment of Medicine/Hematology and Oncology, University of Münster, Münster, Germany.
Astrid JeibmannInstitute of Neuropathology, University Hospital Münster, Münster, Germany.
Jens SchittenhelmDepartment of Neuropathology, Institute of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany.
Camelia-Maria MonoranuInstitute of Pathology, University of Würzburg, Würzburg, Germany.
Andreas RosenwaldInstitute of Pathology, University of Würzburg, Würzburg, Germany.
Martin KortümDepartment of Internal Medicine 2, University Hospital of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0002-7011-0286
Leo RascheDepartment of Internal Medicine 2, University Hospital of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0002-9536-9649
Hermann EinseleDepartment of Internal Medicine 2, University Hospital of Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0002-7680-0819
Philipp T MeyerDepartment of Nuclear Medicine, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Joachim BrumbergDepartment of Nuclear Medicine, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Simon VölklDepartment of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany.
Andreas MackensenDepartment of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany.
Roland CorasDepartment of Neuropathology, University Hospital Erlangen, Erlangen, Germany.
Michael von Bergwelt-BaildonDepartment of Medicine III, Hematology/Oncology, University Hospital, Ludwig-Maximilians Universität (LMU) Munich, Munich, Germany.
Nathalie L AlbertGerman Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Laura M BartosDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.
Matthias BrendelDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.
Adrien HolzgreveDepartment of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-9566-8438
Matthias MackDepartment of Nephrology, University of Regensburg, Regensburg, Germany.ORCID http://orcid.org/0000-0002-3157-7262
Melanie BoerriesInstitute of Medical Bioinformatics and Systems Medicine, Medical Center, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-3670-0602
Crystal L MackallCenter for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6323-4304
Justus DuysterDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Philipp HennekeDivision of Pediatric Infectious Diseases, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Josef PrillerDepartment of Psychiatry, Technischen Universität München (TUM), Munich, Germany.
Natalie KöhlerDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-7502-0431
Felix StrübingCenter for Neuropathology and Prion Research, University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-9436-6294
Bertram BengschDepartment of Medicine II, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-2552-740X
Marco RuellaCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-4301-5811
Marion SubkleweDepartment of Medicine III, Hematology/Oncology, University Hospital, Ludwig-Maximilians Universität (LMU) Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-9154-9469
Louisa von BaumgartenGerman Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-6634-0927
Saar GillCenter for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Marco PrinzInstitute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0349-1955
Robert ZeiserDepartment of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany. robert.zeiser@uniklinik-freiburg.de.ORCID http://orcid.org/0000-0001-6565-3393
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 Joseph Anthony Fraietta · 2017 to 2026
$26.8MMODULATION OF CD5 SIGNALING TO ENHANCE ADOPTIVE T-CELL THERAPIES FOR CANCERR37CA262362 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Marco Ruella · 2022 to 2026
$2.6MDeutsche Forschungsgemeinschaft (German Research Foundation) 872/4-1Deutsche Forschungsgemeinschaft (German Research Foundation) SFB1160Deutsche Forschungsgemeinschaft (German Research Foundation) SFB-1479 - Project ID: 441891347Deutsche Forschungsgemeinschaft (German Research Foundation) TRR 167 Project-ID 259373024Deutsche Krebshilfe (German Cancer Aid) 70114655EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) EU Proposal n° ERC-2022-ADG Project: 101094168NCI NIH HHS P01 CA214278
Abstract
Cancer immunotherapy with chimeric antigen receptor (CAR) T cells can cause immune effector cell-associated neurotoxicity syndrome (ICANS). However, the molecular mechanisms leading to ICANS are not well understood. Here we examined the role of microglia using mouse models and cohorts of individuals with ICANS. CD19-directed CAR (CAR19) T cell transfer in B cell lymphoma-bearing mice caused microglia activation and neurocognitive deficits. The TGFβ-activated kinase-1 (TAK1)-NF-κB-p38 MAPK pathway was activated in microglia after CAR19 T cell transfer. Pharmacological TAK1 inhibition or genetic Tak1 deletion in microglia using Cx3cr1
Indexed as
MAP Kinase Kinase KinasesMicrogliaNeurotoxicity SyndromesReceptors, Chimeric AntigenAnimalsAntigens, CD19FemaleHumansImmunotherapy, AdoptiveLymphoma, B-CellMAP Kinase Kinase Kinase 7MiceNF-kappa Bp38 Mitogen-Activated Protein KinasesSignal TransductionT-LymphocytesAntigens, CD19cell-associated neurotoxicityMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesNF-kappa Bp38 Mitogen-Activated Protein KinasesReceptors, Chimeric Antigen
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PMID
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