Transcriptional states of CAR-T infusion relate to neurotoxicity - lessons from high-resolution single-cell SOM expression portraying.


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.

PubMed ID: 36248848

Projects: imSAVAR - Immune safety avatar: nonclinical mimicking of the immune syst...

Publication type: Journal article

Journal: Front Immunol

Human Diseases: No Human Disease specified

Citation: Front Immunol. 2022 Sep 28;13:994885. doi: 10.3389/fimmu.2022.994885. eCollection 2022.

Date Published: 17th Oct 2022

Registered Mode: by PubMed ID

Authors: H. Loeffler-Wirth, M. Rade, A. Arakelyan, M. Kreuz, M. Loeffler, U. Koehl, K. Reiche, H. Binder


Views: 776

Created: 31st Mar 2023 at 16:25

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