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000157001 1001_ $$0P:(DE-He78)e6c151d449e1db05b1ffb5ad5ec656cf$$aNi, Jing$$b0$$eFirst author
000157001 245__ $$aSingle-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity.
000157001 260__ $$aNew York, NY$$bElsevier$$c2020
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000157001 520__ $$aEnhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Hypoxia is a common feature of solid tumors, and cells adapt by upregulating the transcription factor HIF-1α. Here, we defined the transcriptional landscape of mouse tumor-infiltrating natural killer (NK) cells by using single-cell RNA sequencing. Conditional deletion of Hif1a in NK cells resulted in reduced tumor growth, elevated expression of activation markers, effector molecules, and an enriched NF-κB pathway in tumor-infiltrating NK cells. Interleukin-18 (IL-18) from myeloid cells was required for NF-κB activation and the enhanced anti-tumor activity of Hif1a-/- NK cells. Extended culture with an HIF-1α inhibitor increased human NK cell responses. Low HIF1A expression was associated with high expression of IFNG in human tumor-infiltrating NK cells, and an enriched NK-IL18-IFNG signature in solid tumors correlated with increased overall patient survival. Thus, inhibition of HIF-1α unleashes NK cell anti-tumor activity and could be exploited for cancer therapy.
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000157001 7001_ $$0P:(DE-He78)4759f8845c2e77163b9a1f0191a14821$$aWang, Xi$$b1$$eFirst author
000157001 7001_ $$0P:(DE-He78)6459232320662d60ee842fd348128d87$$aStojanovic, Ana$$b2$$eFirst author
000157001 7001_ $$0P:(DE-He78)4cbe2c7f126a8fe4deb5c1b4d7cdc2ee$$aZhang, Qin$$b3
000157001 7001_ $$aWincher, Marian$$b4
000157001 7001_ $$0P:(DE-He78)491dd1552f3d82e92591b88eec8479aa$$aBühler, Lea Katharina$$b5
000157001 7001_ $$0P:(DE-He78)7c776439971ef21f36ac730cfbff7fff$$aArnold, Annette$$b6
000157001 7001_ $$0P:(DE-HGF)0$$aCorreia, Margareta P$$b7
000157001 7001_ $$aWinkler, Manuel$$b8
000157001 7001_ $$aKoch, Philipp-Sebastian$$b9
000157001 7001_ $$aSexl, Veronika$$b10
000157001 7001_ $$0P:(DE-He78)9dbe272aaadbdc810ab0bb291eae428e$$aHöfer, Thomas$$b11
000157001 7001_ $$0P:(DE-He78)d2b4dd8bdffe4aaa0f5e30e91587766f$$aCerwenka, Adelheid$$b12$$eLast author
000157001 773__ $$0PERI:(DE-600)2001966-X$$a10.1016/j.immuni.2020.05.001$$gVol. 52, no. 6, p. 1075 - 1087.e8$$n6$$p1075 - 1087.e8$$tImmunity$$v52$$x1074-7613$$y2020
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