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Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior anti-tumor activity

ABSTRACT: Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior anti-tumor activity

PROVIDER: PRJNA1051570 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR27185821_1.fastq.gz	Fastqsanger.gz
	SRR27185821_2.fastq.gz	Fastqsanger.gz
	SRR27185822_1.fastq.gz	Fastqsanger.gz
	SRR27185822_2.fastq.gz	Fastqsanger.gz

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Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior anti-tumor activity [scRNA-seq]

Project description:Allogeneic natural killer (NK) cell therapies are a valuable treatment option for cancer, given their remarkable safety and favorable efficacy profile. Although the use of allogeneic donors allows for off-the-shelf and timely patient treatment, intrinsic interindividual differences put clinical efficacy at risk. The identification of donors with superior anti-tumor activity is essential to ensure the success of adoptive NK cell therapies. Here, we investigated the heterogeneity of 10 umbilical cord blood stem cell-derived NK cell batches. First, we evaluated the donors’ cytotoxic potential against tumor cell lines from solid and hematological cancer indications, to distinguish a group of superior, “excellent” killers (4/10), compared to “good” killers (6/10). Next, bulk and single-cell RNA-Sequencing, performed at different stages of NK differentiation, revealed distinct transcriptomic features of the two groups. Excellent donors showed an enrichment in cytotoxicity pathways and a depletion of myeloid traits, linked to the presence of a larger population of effector-like NK cells early on during differentiation. Consequently, we defined a multi-factorial gene expression signature able to predict the donors’ anti-tumor potential. Our study contributes to the identification of key traits of superior NK cell batches, supporting the development of efficacious NK therapeutics and the achievement of durable anti-tumor responses

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Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior anti-tumor activity [Bulk RNA-seq]

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Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior anti-tumor activity [scRNA-seq]

Project description:Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior anti-tumor activity [scRNA-seq]

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Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior anti-tumor activity [Bulk RNA-seq]

Project description:Bulk and single-cell transcriptomics identify gene signatures of stem cell-derived NK cell donors with superior anti-tumor activity [Bulk RNA-seq]

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Microarray comparison of NK cell from healthy donors and day 14 post stem cell transplantation

Project description:NK cells were first isolated from PBMCs using EasySepâ¢ Human NK cell enrichment kit (STEMCELL biotechnology). The magnetically isolated NK cells were stained with anti-CD3 FITC, anti-CD56 Pe-Cy7 and LIVE/DEADÂ® red stain for a further enrichment, whereby the CD3 negative and CD56 positive live cells were sorted with MoFloâ¢ cell sorter (Beckman Coulter). The sorted NK cell populations were sent to AROS Applied Biotechnology A/S (Aarhus N, Denmark) to be analysed using GeneChipÂ® Human Transcriptome Array 2.0 (Affymetrix, USA). The transcription profile of NK cells from day 14 post stem cell transplantation was compared with those from healthy donors.

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