Natural killer cell antitumor activity is under transcriptional control
The transcription factors that control natural killer (NK) cell differentiation, like EOMES and T-BET, influence their antimetastatic tumor response in mouse models.
NK cells can promote CD8 T cell immunity in solid tumors by producing chemokines that recruit dendritic cells that present antigen to T cells.
IKAROS represses the expression of the proapoptotic protein BIM to promote the survival of differentiated NK cells and promotes expression of activator protein (AP)-1 proteins.
Inhibitors of the AP-1 family transcription factors, BACH2 and BATF, limit the response of NK cells to leukemia in humans, and metastatic melanoma in mice.
The hypoxic tumor microenvironment induces the transcription factor HIF1α in NK cells, resulting in reduced NF-kB activity and IFN-γ-production, and altered recruitment of myeloid cells. Therefore, targeting HIF1α could improve NK cell responses in solid tumors.
https://www.cell.com/trends/immunology/fulltext/S1471-4906(25)00217-0
