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Transcription factor Zhx2 restricts NK cell maturation and suppresses their antitumor immunity
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Tan, SY (författare)
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Guo, XW (författare)
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Li, MZ (författare)
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Wang, TX (författare)
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Wang, ZH (författare)
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Li, CY (författare)
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Wu, ZC (författare)
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- Li, NL (författare)
- Karolinska Institutet
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Gao, LF (författare)
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Liang, XH (författare)
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Ma, CH (författare)
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(creator_code:org_t)
- 2021-07-19
- 2021
- Engelska.
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 218:9
- Relaterad länk:
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http://kipublication...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 (Zhx2Δ/Δ) 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.
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- Av författaren/redakt...
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Tan, SY
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Guo, XW
-
Li, MZ
-
Wang, TX
-
Wang, ZH
-
Li, CY
-
visa fler...
-
Wu, ZC
-
Li, NL
-
Gao, LF
-
Liang, XH
-
Ma, CH
-
visa färre...
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The Journal of e ...
- Av lärosätet
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Karolinska Institutet