| First Author | Bi J | Year | 2021 |
| Journal | Sci Adv | Volume | 7 |
| Issue | 38 | Pages | eabi6515 |
| PubMed ID | 34524845 | Mgi Jnum | J:311633 |
| Mgi Id | MGI:6766138 | Doi | 10.1126/sciadv.abi6515 |
| Citation | Bi J, et al. (2021) TIPE2 is a checkpoint of natural killer cell maturation and antitumor immunity. Sci Adv 7(38):eabi6515 |
| abstractText | The maturation process of NK cells determines their functionality during which IL-15 plays a critical role. However, very few checkpoints specifically targeting this process have been discovered. Here, we report that TIPE2 expression gradually increased during NK cell ontogenesis correlating to their maturation stages in both mice and humans. NK-specific TIPE2 deficiency increased mature NK cells in mice, and these TIPE2-deficient NK cells exhibited enhanced activation, cytotoxicity, and IFN-ï§ production upon stimulation and enhanced response to IL-15 for maturation. Moreover, TIPE2 suppressed IL-15âtriggered mTOR activity in both human and murine NK cells. Consequently, blocking mTOR constrained the effect of TIPE2 deficiency on NK cell maturation in response to IL-15. Last, NK-specific TIPE2-deficient mice were resistant to tumor growth in vivo. Our results uncover a potent checkpoint in NK cell maturation and antitumor immunity in both mice and humans, suggesting a promising approach of targeting TIPE2 for NK cellâbased immunotherapies. |
