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Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR‐engineered T cells
- Source :
- European Journal of Immunology. 51:1992-2005
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (TSCM ) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-TSCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.
- Subjects :
- 0301 basic medicine
Coronavirus disease 2019 (COVID-19)
T-Lymphocytes
Adoptive T-cell therapy
Immunology
Population
Receptors, Antigen, T-Cell
Computational biology
Biology
Immunotherapy, Adoptive
Immunophenotyping
Flow cytometry
03 medical and health sciences
0302 clinical medicine
High-dimensional analysis
medicine
Data Mining
Humans
Immunology and Allergy
education
Data limited
education.field_of_study
Receptors, Chimeric Antigen
medicine.diagnostic_test
SARS-CoV-2
Immune exhaustion
T-cell receptor
COVID-19
Flow Cytometry
Phenotype
030104 developmental biology
Cytokines
Genetic Engineering
Immunologic Memory
Cytometry
Function (biology)
030215 immunology
Subjects
Details
- ISSN :
- 15214141 and 00142980
- Volume :
- 51
- Database :
- OpenAIRE
- Journal :
- European Journal of Immunology
- Accession number :
- edsair.doi.dedup.....9e0332e0a0161061c4043c82b23ad15c