Targeting TGFβ-activated kinase-1 activation in microglia reduces CAR T immune effector cell-associated neurotoxicity syndrome.

Journal

Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119

Informations de publication

Date de publication:
13 May 2024
Historique:
received: 18 04 2023
accepted: 27 03 2024
medline: 14 5 2024
pubmed: 14 5 2024
entrez: 13 5 2024
Statut: aheadofprint

Résumé

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

Identifiants

DOI: 10.1038/s43018-024-00764-7 PMID: 38741011
pubmed: 38741011
doi: 10.1038/s43018-024-00764-7
pii: 10.1038/s43018-024-00764-7
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TRR 167 Project-ID 259373024
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB-1479 - Project ID: 441891347
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB1160
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 872/4-1
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : EU Proposal n° ERC-2022-ADG Project: 101094168
Organisme : Deutsche Krebshilfe (German Cancer Aid)
ID : 70114655

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Janaki Manoja Vinnakota (JM)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany.

Francesca Biavasco (F)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Marius Schwabenland (M)

Institute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0003-2205-5427

Chintan Chhatbar (C)

Institute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.

Rachael C Adams (RC)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Daniel Erny (D)

Institute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0001-6000-8838

Sandra Duquesne (S)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Nadia El Khawanky (N)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Medicine III, School of Medicine, Technical University of Munich, Munich, Germany.
Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.

Dominik Schmidt (D)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany.
ORCID: 0000-0002-7744-1248

Viktor Fetsch (V)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany.

Alexander Zähringer (A)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Henrike Salié (H)

Department of Medicine II, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0002-2993-3782

Dimitrios Athanassopoulos (D)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Lukas M Braun (LM)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, Albert-Ludwigs-University, Freiburg, Germany.
ORCID: 0000-0003-0770-4994

Nora R Javorniczky (NR)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Jenny N H G Ho (JNHG)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Katrin Kierdorf (K)

Institute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0002-9272-4780

Reinhard Marks (R)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Ralph Wäsch (R)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0002-0813-3444

Federico Simonetta (F)

Division of Hematology, Geneva University Hospitals Geneva, Geneva, Switzerland.

Geoffroy Andrieux (G)

Institute of Medical Bioinformatics and Systems Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0002-5389-9481

Dietmar Pfeifer (D)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Gianni Monaco (G)

Institute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Single-Cell Omics Platform Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Institute for Transfusion Medicine and Gene Therapy, Medical Center, University of Freiburg, Freiburg, Germany.

Christian Capitini (C)

Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-2276-6731

Terry J Fry (TJ)

Center for Cancer and Blood Disorders, Children's Hospital Colorado and Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
ORCID: 0000-0001-8044-5226

Thomas Blank (T)

Institute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0002-3969-405X

Bruce R Blazar (BR)

Masonic Cancer Center and Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular Therapy, University of Minnesota, Minneapolis, MN, USA.
ORCID: 0000-0002-9608-9841

Eva Wagner (E)

Department of Hematology and Medical Oncology, Johannes Gutenberg-University Medical Center, Mainz, Germany.
ORCID: 0000-0002-0728-2253

Matthias Theobald (M)

Department of Hematology and Medical Oncology, Johannes Gutenberg-University Medical Center, Mainz, Germany.

Clemens Sommer (C)

Institute of Neuropathology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Matthias Stelljes (M)

Department of Medicine/Hematology and Oncology, University of Münster, Münster, Germany.

Christian Reicherts (C)

Department of Medicine/Hematology and Oncology, University of Münster, Münster, Germany.

Astrid Jeibmann (A)

Institute of Neuropathology, University Hospital Münster, Münster, Germany.

Jens Schittenhelm (J)

Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital Tübingen, Tübingen, Germany.

Camelia-Maria Monoranu (CM)

Institute of Pathology, University of Würzburg, Würzburg, Germany.

Andreas Rosenwald (A)

Institute of Pathology, University of Würzburg, Würzburg, Germany.

Martin Kortüm (M)

Department of Internal Medicine 2, University Hospital of Würzburg, Würzburg, Germany.
ORCID: 0000-0002-7011-0286

Leo Rasche (L)

Department of Internal Medicine 2, University Hospital of Würzburg, Würzburg, Germany.
ORCID: 0000-0002-9536-9649

Hermann Einsele (H)

Department of Internal Medicine 2, University Hospital of Würzburg, Würzburg, Germany.
ORCID: 0000-0002-7680-0819

Philipp T Meyer (PT)

Department of Nuclear Medicine, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Joachim Brumberg (J)

Department of Nuclear Medicine, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Simon Völkl (S)

Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany.

Andreas Mackensen (A)

Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Erlangen, Germany.

Roland Coras (R)

Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.

Michael von Bergwelt-Baildon (M)

Department of Medicine III, Hematology/Oncology, University Hospital, Ludwig-Maximilians Universität (LMU) Munich, Munich, Germany.

Nathalie L Albert (NL)

German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.

Laura M Bartos (LM)

Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.

Matthias Brendel (M)

Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.
German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Adrien Holzgreve (A)

Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany.
ORCID: 0000-0002-9566-8438

Matthias Mack (M)

Department of Nephrology, University of Regensburg, Regensburg, Germany.
ORCID: 0000-0002-3157-7262

Melanie Boerries (M)

Institute of Medical Bioinformatics and Systems Medicine, Medical Center, University of Freiburg, Freiburg, Germany.
German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0002-3670-0602

Crystal L Mackall (CL)

Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford, CA, USA.
ORCID: 0000-0001-6323-4304

Justus Duyster (J)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Philipp Henneke (P)

Division of Pediatric Infectious Diseases, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Josef Priller (J)

Department of Psychiatry, Technischen Universität München (TUM), Munich, Germany.

Natalie Köhler (N)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany.
ORCID: 0000-0002-7502-0431

Felix Strübing (F)

Center for Neuropathology and Prion Research, University Hospital, LMU Munich, Munich, Germany.
ORCID: 0000-0002-9436-6294

Bertram Bengsch (B)

Department of Medicine II, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0003-2552-740X

Marco Ruella (M)

Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
ORCID: 0000-0003-4301-5811

Marion Subklewe (M)

Department of Medicine III, Hematology/Oncology, University Hospital, Ludwig-Maximilians Universität (LMU) Munich, Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0001-9154-9469

Louisa von Baumgarten (L)

German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Neuro-Oncology, Department of Neurosurgery, University Hospital, LMU Munich, Munich, Germany.
ORCID: 0000-0002-6634-0927

Saar Gill (S)

Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, PA, USA.
Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Marco Prinz (M)

Institute for Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Signalling Research Centres BIOSS and Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany.
ORCID: 0000-0002-0349-1955

Robert Zeiser (R)

Department of Medicine I, Medical Centre, Faculty of Medicine, University of Freiburg, Freiburg, Germany. robert.zeiser@uniklinik-freiburg.de.
German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany. robert.zeiser@uniklinik-freiburg.de.
Signalling Research Centres BIOSS and Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany. robert.zeiser@uniklinik-freiburg.de.
ORCID: 0000-0001-6565-3393

Classifications MeSH