| First Author | Tan S | Year | 2021 |
| Journal | J Exp Med | Volume | 218 |
| Issue | 9 | PubMed ID | 34279541 |
| Mgi Jnum | J:331170 | Mgi Id | MGI:6887338 |
| Doi | 10.1084/jem.20210009 | Citation | Tan S, et al. (2021) Transcription factor Zhx2 restricts NK cell maturation and suppresses their antitumor immunity. J Exp Med 218(9):e20210009 |
| abstractText | The maturation and functional competence of natural killer (NK) cells is a tightly controlled process that relies on transcription factors (TFs). Here, we identify transcriptional repressor zinc fingers and homeoboxes 2 (Zhx2) as a novel regulator that restricts NK cell maturation and function. Mice with Zhx2 conditional deletion in NK cells (Zhx2Delta/Delta) showed accumulation of matured NK cells. Loss of Zhx2 enhanced NK cell survival and NK cell response to IL-15. Transcriptomic analysis revealed Zeb2, a key TF in NK cell terminal maturation, as a direct downstream target of Zhx2. Therapeutically, transfer of Zhx2-deficient NK cells resulted in inhibition of tumor growth and metastasis in different murine models. Our findings collectively unmask a previously unrecognized role of Zhx2 as a novel negative regulator in NK cell maturation and highlight its therapeutic potential as a promising strategy to enhance NK cell-mediated tumor surveillance. |
