TOPLINE:

Genome-wide CRISPR screens in primary human natural killer (NK) cells identified critical checkpoints regulating resistance to immunosuppressive pressures in the tumor microenvironment. Targeted knockout of MED12 , ARIH2 , and CCNC enhanced NK cell antitumor activity against multiple treatment-refractory human cancers, improving both innate and chimeric antigen receptor (CAR)-mediated NK cell function.

METHODOLOGY:

Researchers performed multiple genome-wide CRISPR screens in primary human NK cells to identify critical checkpoints regulating resistance to immunosuppressive pressures.

Analysis included screening of 19,281 genes using 77,736 unique guide RNA sequences along with 500 nontargeting control guides.

Investigation focused on ablation of MED12 , ARIH2 , and

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