Loeffler-Wirth, Henry
[VerfasserIn];
Rade, Michael
[VerfasserIn];
Arakelyan, Arsen
[VerfasserIn];
Kreuz, Markus
[VerfasserIn];
Loeffler, Markus
[VerfasserIn];
Koehl, Ulrike
[VerfasserIn];
Reiche, Kristin
[VerfasserIn];
Binder, Hans
[VerfasserIn]
Transcriptional states of CAR-T infusion relate to neurotoxicity
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Medientyp:
E-Artikel
Titel:
Transcriptional states of CAR-T infusion relate to neurotoxicity
:
lessons from high-resolution single-cell SOM expression portraying
Beteiligte:
Loeffler-Wirth, Henry
[VerfasserIn];
Rade, Michael
[VerfasserIn];
Arakelyan, Arsen
[VerfasserIn];
Kreuz, Markus
[VerfasserIn];
Loeffler, Markus
[VerfasserIn];
Koehl, Ulrike
[VerfasserIn];
Reiche, Kristin
[VerfasserIn];
Binder, Hans
[VerfasserIn]
Erschienen:
Lausanne: Frontiers Media S.A., [2024]
Erschienen in:Frontiers in Immunology ; 13, (2022)
Beschreibung:
Anti-CD19 CAR-T cell immunotherapy is a hopeful treatment option forpatients with B cell lymphomas, however it copes with partly severe adverseeffects like neurotoxicity. Single-cell resolved molecular data sets incombination with clinical parametrization allow for comprehensivecharacterization of cellular subpopulations, their transcriptomic states, andtheir relation to the adverse effects. We here present a re-analysis of single-cellRNA sequencing data of 24 patients comprising more than 130,000 cells withfocus on cellular states and their association to immune cell relatedneurotoxicity. For this, we developed a single-cell data portraying workflowto disentangle the transcriptional state space with single-cell resolution and itsanalysis in terms of modularly-composed cellular programs. We demonstratedcapabilities of single-cell data portraying to disentangle transcriptional statesusing intuitive visualization, functional mining, molecular cell stratification, andvariability analyses. Our analysis revealed that the T cell composition of thepatient’s infusion product as well as the spectrum of their transcriptional statesof cells derived from patients with low ICANS grade do not markedly differ fromthose of cells from high ICANS patients, while the relative abundancies,particularly that of cycling cells, of LAG3-mediated exhaustion and of CARpositive cells, vary. Our study provides molecular details of the transcriptomiclandscape with possible impact to overcome neurotoxicity.