Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion.
Sci. Adv. 9:eadg3919 (2023)
Prolonged cytopenias after chimeric antigen receptor (CAR) T cell therapy are a significant clinical problem and the underlying pathophysiology remains poorly understood. Here, we investigated how (CAR) T cell expansion dynamics and serum proteomics affect neutrophil recovery phenotypes after CD19-directed CAR T cell therapy. Survival favored patients with "intermittent" neutrophil recovery (e.g., recurrent neutrophil dips) compared to either "quick" or "aplastic" recovery. While intermittent patients displayed increased CAR T cell expansion, aplastic patients exhibited an unfavorable relationship between expansion and tumor burden. Proteomics of patient serum collected at baseline and in the first month after CAR-T therapy revealed higher markers of endothelial dysfunction, inflammatory cytokines, macrophage activation, and T cell suppression in the aplastic phenotype group. Prolonged neutrophil aplasia thus occurs in patients with systemic immune dysregulation at baseline with subsequently impaired CAR-T expansion and myeloid-related inflammatory changes. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cytokine Release Syndrome; Stem-cell Boost; B-cell; Infectious Complications; Axicabtagene Ciloleucel; Interferon-gamma; Responses; Promotes; Interleukin-15; Inflammation
ISSN (print) / ISBN
2375-2548
e-ISSN
2375-2548
Journal
Science Advances
Quellenangaben
Volume: 9,
Issue: 38,
Article Number: eadg3919
Publisher
American Association for the Advancement of Science (AAAS)
Publishing Place
Washington, DC [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Metabolomics & Proteomics (CF-MPC)
Grants
Bavarian Cancer Research Center (BZKF)
ElseKroner-Fresenius Stiftung
Wilhelm-Sander Stiftung
Bavarian Elite Graduate Training Network
DFG
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Bruno & Helene Joster Foundation
Gilead Research Scholar Program
Else Kroner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP)
School of Oncology of the German Cancer Consortium (DKTK)
ElseKroner-Fresenius Stiftung
Wilhelm-Sander Stiftung
Bavarian Elite Graduate Training Network
DFG
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Bruno & Helene Joster Foundation
Gilead Research Scholar Program
Else Kroner Forschungskolleg (EKFK) within the Munich Clinician Scientist Program (MCSP)
School of Oncology of the German Cancer Consortium (DKTK)