Anti-CD19 CAR-T cell immunotherapy is a hopeful treatment option for
patients with B cell lymphomas, however it copes with partly severe adverse
effects like neurotoxicity. Single-cell resolved molecular data sets in
combination with clinical parametrization allow for comprehensive
characterization of cellular subpopulations, their transcriptomic states, and
their relation to the adverse effects. We here present a re-analysis of single-cell
RNA sequencing data of 24 patients comprising more than 130,000 cells with
focus on cellular states and their association to immune cell related
neurotoxicity. For this, we developed a single-cell data portraying workflow
to disentangle the transcriptional state space with single-cell resolution and its
analysis in terms of modularly-composed cellular programs. We demonstrated
capabilities of single-cell data portraying to disentangle transcriptional states
using intuitive visualization, functional mining, molecular cell stratification, and
variability analyses. Our analysis revealed that the T cell composition of the
patient’s infusion product as well as the spectrum of their transcriptional states
of cells derived from patients with low ICANS grade do not markedly differ from
those of cells from high ICANS patients, while the relative abundancies,
particularly that of cycling cells, of LAG3-mediated exhaustion and of CAR
positive cells, vary. Our study provides molecular details of the transcriptomic
landscape with possible impact to overcome neurotoxicity.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:90296 |
| Date | 04 March 2024 |
| Creators | Loeffler-Wirth, Henry, Rade, Michael, Arakelyan, Arsen, Kreuz, Markus, Loeffler, Markus, Koehl, Ulrike, Reiche, Kristin, Binder, Hans |
| Publisher | Frontiers Media S.A. |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 994885 |
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