Genome-wide CRISPR screen reveals cancer cell resistance to NK cells induced by NK-derived IFN-gamma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA579227 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10338906.fastq.gz | Fastqsanger.gz | |||
| SRR10338907.fastq.gz | Fastqsanger.gz | |||
| SRR10338908.fastq.gz | Fastqsanger.gz | |||
| SRR10338909.fastq.gz | Fastqsanger.gz | |||
| SRR10338910.fastq.gz | Fastqsanger.gz |
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Project description:Therefore, to gain a deeper understanding of the interaction between NK cells and B-cell malignancies, we performed here a genome-wide CRISPR screen in the 721.221 cell line (referred to as 221), an EBV-transformed lymphoblastoid B-cell line. This cell line had been selected for the loss of classical HLA-I genes [14] and is therefore sensitive to lysis by NK cells. As expected, the loss of ligands for NK activation receptors resulted in reduced sensitivity. However, deletion of a few other genes, including Signal Peptide Peptidase-Like 3 (SPPL3), had the greatest impact on resistance to lysis by NK cells. Here, we describe how SPPL3 is a crucial controller of the interaction between NK cells and their targets. We found that the increased amount of complex N-glycans in SPPL3-deleted tumor cells limits the binding of NK cell receptors and facilitates immune evasion. We further identified glycosyl transferases that were responsible for the resistant phenotype through a secondary screen in SPPL3-deleted cells and analysis of mutations that restored sensitivity to lysis by NK cells.
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