Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CAR+ and CAR- T cells differentiate into an NK-like subset that is associated with increased inflammatory cytokines following infusion

ABSTRACT: CAR+ and CAR- T cells differentiate into an NK-like subset that is associated with increased inflammatory cytokines following infusion

PROVIDER: PRJNA931739 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23343645.fastq.gz	Fastqsanger.gz
	SRR23343646.fastq.gz	Fastqsanger.gz
	SRR23343647_1.fastq.gz	Fastqsanger.gz
	SRR23343647_2.fastq.gz	Fastqsanger.gz
	SRR23343648_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 37

Similar Datasets

Targeted scRNA-seq and AbSeq of human CAR-T cell infusion product from 28 cancer patients

Project description:Immunotherapy using CD19-directed chimeric antigen receptor (CAR)-T cells has shown excellent results for treatment of B-cell leukaemia and lymphoma. To produce CAR-T cells, the patient’s own T cells are isolated from the blood and modified in a laboratory with a genetic vector to express a tumor antigen-directed CAR on its surface. The CAR-T cells are then expanded in numbers and given back to the patient with the aim to eradicate the tumors. However, some patients display primary resistance to CAR-T treatment while others relapse quickly after CAR-T treatment. In this experiment, we seek to understand whether the quality of the individual CAR-T cell product the patients were given can predict outcome to the therapy. We investigate the transcriptional profile of the individual CAR-T infusion products using single-cell RNA sequencing. In this dataset, we identified a T cell subset correlating with response that could be used as an indicator for clinical outcome. Targeted RNA and protein single-cell libraries were obtained using the BD Rhapsody platform (BD Biosciences). In total four separate targeted libraries were produced with 6 patients per library. Sequencing was performed on NovaSeq 6000 S1 sequencer at the SNP&SEQ Technology Platform (Uppsala, Sweden). The raw scRNA-seq data was pre-processed by BD Biosciences using the Rhapsody Analysis pipeline to convert the raw reads into Unique Molecular Identifier (UMI) counts. UMIs are further adjusted within Rhapsody by applying BD’s Recursive Substitution Error Correction (RSEC) and Distribution-Based Error Correction (DBEC) in order to remove false UMIs caused by sequencing or library preparation errors. Pooled samples were deconvoluted using Sample-tag reads. The scRNA-seq and AbSeq counts were loaded, processed and used for clustering and differential gene expression with Seurat v. 4.0.0.

2023-07-24 | E-MTAB-12407 | biostudies-arrayexpress

CAR+ and CAR- T cells differentiate into an NK-like subset that is associated with increased inflammatory cytokines following infusion

Project description:Our understanding of cell fate decisions in hematopoietic stem cells is incomplete. Here, we show that the transcription factor Helios is highly expressed in murine hematopoietic stem and progenitor cells (HSPCs), where it is required to suppress the separation of the platelet/megakaryocyte lineage from the HSPC pool. Helios acts mainly in quiescent cells, where it directly represses the megakaryocyte gene expression program in cells as early as the stem cell stage. Helios binding promotes chromatin compaction, notably at the regulatory regions of platelet-specific genes recognized by the Gata2 and Runx1 transcriptional activators, implicated in megakaryocyte priming. Helios null HSPCs are biased toward the megakaryocyte lineage at the expense of the lymphoid and partially resemble cells of aging animals. We propose that Helios acts as a guardian of HSPC pluripotency by continuously repressing the megakaryocyte fate, which in turn allows downstream lymphoid priming to take place. These results highlight the importance of negative and positive priming events in lineage commitment.

2023-09-26 | GSE224550 | GEO

Single-cell antigen-specific landscape of CAR T infusion product identifies determinants of CD19-positive relapse in patients with ALL

Project description:We report 101,326 single cell transcriptomes and surface protein landscape from the Chimeric antigen receptor-modified (CAR) T infusion products of 12 pediatric ALL patients upon CAR antigen-specific stimulation in comparison with TCR-mediated activation and controls.

2022-06-08 | GSE197215 | GEO

Single-cell RNA sequencing of human CAR-NK cells before infusion and after tumor cells challenge in mice model

Project description:We profiled the transcriptomes of human CD5 CAR-NK cells at the single-cell level to compare the pre-infusion state with the post-challenge state.

2026-07-24 | GSE339022 | GEO

Project description:Chimeric antigen receptor (CAR) therapy targeting CD19 is an effective treatment for refractory B cell malignancies, especially acute lymphoblastic leukemia (ALL). While a majority of patients will achieve a complete response following a single infusion of CD19 CAR T cells, the broad applicability of this treatment is hampered by severe cytokine release syndrome (CRS), which is characterised by fever, hypotension and respiratory insufficiency associated with elevated serum cytokines including interleukin-6 (IL-6). CRS usually occurs within days of T cell infusion at the peak of CAR T cell expansion. In ALL, it is most frequent and more severe in patients with high tumour burden CRS is often responsive to IL-6 receptor blockade, but may require intensive life support and further treatment with high dose corticosteroids to prevent potentially lethal severity. Improved therapeutic and preventive treatments require a better understanding of CRS physiopathology, which has so far remained elusive. We report here a murine model of CRS that develops within 2-3 days of CAR T cell infusion, may be lethal and is responsive to IL-6 receptor blockade. We show that its severity is mediated not by CAR T cell-derived cytokines but by IL-6, interleukin-1 (IL-1) and Nitric Oxide (NO) produced by recipient macrophages. This CRS mechanism enables novel therapeutic interventions.

2018-05-28 | GSE111236 | GEO

Single-cell transcriptomics of chimeric antigen receptor (CAR) T cell infusion products

Project description:Adoptive immunotherapy with T cells expressing chimeric antigen receptors (CARs) for B-cell malignancies serves as a model for identifying subsets with superior clinical activity. We profiled the infusion products (IP) of 9 patients with large B-cell lymphoma (LBCL) using scRNA-sequencing to reveal the therapeutic potential of CD19-specific CAR+ T cells. ScRNA-seq demonstrated that T cells from responders were enriched in pathways related to T-cell killing, migration and actin cytoskeleton, and TCR clustering.

2023-03-12 | GSE208052 | GEO

Single cell RNA sequencing of CD19 CAR T-cell infusion products

Project description:We performed single cell RNA sequencing of remnants from CD19 CAR T-cell infusion products used for standard of care treatment for relapsed/refractory large B-cell lymphoma. Libraries were prepared using 10X 5Ã¢Â€Â™ GEX chemistry and sequenced on an Illumina HiSeq 4000 to obtain >50,000 reads per cell.

| EGAS00001004576 | EGA

Cerebrospinal Fluid Proteomics Exerts Prognostic Potential for ICANS in CAR-T Therapy

Project description:We intended to find biomarkers for ICANS by comprehensive high-throughput proteomics profiling of CSF collected before CAR-T infusion.

2025-05-14 | PXD052238 | JPOST Repository

Single cell RNA-seq analysis of bone marrow (BM) samples of patients with B-Cell Acute Lymphoblastic Leukemia treated with anti CD19 CAR T cells

Project description:Single-cell RNA sequencing of BM resident immune cells of patients undergoing CAR T-cell infusion and their Infusion Product (IP). Data in this study were generated from a patients enrolled in the FT01CARCIK Phase I/IIb clinical trial (NCT03389035) and two patients treated with autologous commercial CAR T cells (tisagenlecleucel). BM samples have been collected before CAR T treatment (pre) and at early time points (1-2 months) after treatment (post). CD45+CD3+ T cells, and CD45+/lowCD3-, encompassing the hematopoietic immune niche of the TME cells, have been separated by flow cytometry-based cell sorting and compared to cells of the corresponding patient’s BM before CAR T-cell treatment at the moment of relapse. In parallel, CAR T-cell infusion products (IP) have been sorted according to the surface CAR expression. Significance: This study highlights the critical role of the tumor microenvironment on CAR T-cell fate and endogenous immunity in B-cell acute lymphoblastic leukemia. We demonstrate that IFN response, hypoxia, and TGF-b signaling lead to general immune suppression, resulting in endogenous T-cell exhaustion and compromising CAR T-cell efficacy

2025-12-31 | E-MTAB-14549 | biostudies-arrayexpress

Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission

Project description:Despite a high response rate in chimeric antigen receptor (CAR) T therapy for acute lymphocytic leukemia (ALL), approximately 50% of patients relapse within the first year, representing an urgent question to address in the next stage of cellular immunotherapy. To investigate the molecular determinants of ultra-long CAR T persistence, we obtained single-cell multi-omics sequencing data from 695,819 pre-infusion CAR T cells at the basal level or upon CAR-specific stimulation from 82 pediatric ALL patients enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type-2 functionality in CAR T infusion products was significantly associated with patients maintaining a median B-cell aplasia duration of 8.4 years. Analysis of ligand-receptor interactions unveiled that type-2 cells regulate a distinct dysfunctional population, and the addition of IL-4 during antigen-specific activation alleviates CAR T cell dysfunction while enhancing functional fitness at both transcriptomic and epigenomic levels. Serial proteomic profiling of post-infusion sera revealed a higher level of circulating type-2 cytokines in 5-year or 8-year relapse-free responders. In a leukemic mouse model, type-2 high CAR T products demonstrated superior expansion and antitumor activity particularly upon leukemia rechallenge. Restoring antitumor efficacy in type-2 low CAR T cells was attainable by enhancing their type-2 functionality, either through incorporating IL-4 into the manufacturing process or priming manufactured CAR T products with IL-4 prior to infusion. Our findings provide key insights into the mediators of CAR T longevity and suggest potential therapeutic strategies to sustain long-term remission by boosting type-2 functionality in CAR T cells.

2024-05-27 | GSE262072 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data