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

ABSTRACT: Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer^1-3. However, the molecular mechanisms that regulate CAR-NK cell activity remain unclear. Here we identify the transcription factor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function. Transcriptomic analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector function after adoptive transfer in a tumour mouse model, and this peak coincided with signatures of both activation and dysfunction. We demonstrate that both CAR activation and interleukin-15 signalling rapidly induce CREM upregulation in NK cells. Functionally, CREM deletion enhances CAR-NK cell effector function both in vitro and in vivo and

SUBMITTER: Rafei H 

PROVIDER: S-EPMC12286855 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature