ArticleJournal for immunotherapy of cancer2023
Characterization of the endotheliopathy, innate-immune activation and hemostatic imbalance underlying CAR-T cell toxicities: laboratory tools for an early and differential diagnosis.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Coordinated expansion of CD163bioRxiv : the preprint server for biology · 2026Article
- Haemostatic changes during CART cell therapy and risk of complications.Cancer immunology, immunotherapy : CII · 2026Article
- Complement system in cancer: friend or foe of immunotherapy.Journal for immunotherapy of cancer · 2026Review
- Critical complications in cancer patients admitted to the ICU in the era of immunotherapy: recognition, differential diagnosis, and management.Frontiers in medicine · 2026Review
- Endotheliopathy in CAR T-Cell Therapy: Mechanistic Insights into the VWF/ADAMTS13 Axis and the Angiopoietin-Tie2 Pathway.TH open : companion journal to thrombosis and haemostasis · 2026Review
- Review
- Immunotherapy-associated hemostatic abnormalities: bleeding and thrombotic complications.Annals of hematology · 2025Review
- Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025Review
- Leucine-rich α-2 glycoprotein 1 (LRG1) during inflammatory complications after allogeneic stem cell transplantation and CAR-T cell therapy.Journal for immunotherapy of cancer · 2025Article
- m-EASIX (better than EASIX) predicts severe CAR T-cell toxicities, worse overall survival, and discriminates cytokine release syndrome from sepsis.Frontiers in immunology · 2025Article
- Endothelial dysfunction and hemostatic imbalance in CAR T-cell-associated toxicities: pathophysiological insights and the role of circulating biomarkers.Frontiers in immunology · 2025Review
- CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities.Brain sciences · 2024Review
- Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives.Frontiers in immunology · 2024Review
- Valsartan attenuates LPS-induced ALI by modulating NF-κB and MAPK pathways.Frontiers in pharmacology · 2024Article
- Endothelial activation and damage as a common pathological substrate in different pathologies and cell therapy complications.Frontiers in medicine · 2023Review
- Immune effector cell-associated neurotoxicity syndrome: integrative mechanisms, predictive biomarkers, and translational pathways for prevention in CAR T-cell therapy.Frontiers in neurologyReview
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChimeric antigen receptor (CAR)-T cell-based immunotherapy constitutes a revolutionary advance for treatment of relapsed/refractory hematological malignancies. Nevertheless, cytokine release and immune effector cell-associated neurotoxicity syndromes are life-threatening toxicities in which the endothelium could be a pathophysiological substrate. Furthermore, differential diagnosis from sepsis, highly incident in these patients, is challenging. Suitable laboratory tools could be determinant for their appropriate management.
methodsSixty-two patients treated with CAR-T cell immunotherapy for hematological malignancies (n=46 with CD19-positive diseases, n=16 with multiple myeloma) were included. Plasma samples were obtained: before CAR-T cell infusion (baseline); after 24-48 hours; at suspicion of any toxicity onset and 24-48 hours after immunomodulatory treatment. Biomarkers of endothelial dysfunction (soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble TNF receptor 1 (sTNFRI), thrombomodulin (TM), soluble suppression of tumorigenesis-2 factor (ST2), angiopoietin-2 (Ang-2)), innate immunity activation (neutrophil extracellular traps (NETs), soluble C5b-9 (sC5b-9)) and hemostasis/fibrinolysis (von Willebrand Factor antigen (VWF:Ag), ADAMTS-13 (A13), α2-antiplasmin (α2-AP), plasminogen activator inhibitor-1 antigen (PAI-1 Ag)) were measured and compared with those in cohorts of patients with sepsis and healthy donors.
resultsPatients who developed CAR-T cell toxicities presented increased levels of sVCAM-1, sTNFRI and ST2 at the clinical onset versus postinfusion values. Twenty-four hours after infusion, ST2 levels were good predictors of any CAR-T cell toxicity, and combination of ST2, Ang-2 and NETs differentiated patients requiring intensive care unit admission from those with milder clinical presentations. Association of Ang-2, NETs, sC5b-9, VWF:Ag and PAI-1 Ag showed excellent discrimination between severe CAR-T cell toxicities and sepsis.
conclusionsThis study provides relevant contributions to the current knowledge of the CAR-T cell toxicities pathophysiology. Markers of endotheliopathy, innate immunity activation and hemostatic imbalance appear as potential laboratory tools for their prediction, severity and differential diagnosis.
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