CREM is a regulatory checkpoint of CAR and IL-15 signaling in NK cells

This is a preclinical study investigating the role of CREM transcription factor in CAR NK cells. We found thata CREM is a regulatory checkpoint induced by CAR CD3z signaling and IL-15 stimulation that leads to suppression of NK cell function. CREM KO enhances the anti-tumor efficacy of CAR NK cells. Overall design: Multiple in vitro and in vivo experiments were conducted to establish the role of CREM in CAR NK cells. Mechanistic assays such as with phosphorylation studies, and transcriptomic (bulk RNA seq) and epigenetic (bulk ATAC and ChIP seq) analyses were conducted.