%0 Journal Article
%A Ni, Jing
%A Wang, Xi
%A Stojanovic, Ana
%A Zhang, Qin
%A Wincher, Marian
%A Bühler, Lea Katharina
%A Arnold, Annette
%A Correia, Margareta P
%A Winkler, Manuel
%A Koch, Philipp-Sebastian
%A Sexl, Veronika
%A Höfer, Thomas
%A Cerwenka, Adelheid
%T Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity.
%J Immunity
%V 52
%N 6
%@ 1074-7613
%C New York, NY
%I Elsevier
%M DKFZ-2020-01298
%P 1075 - 1087.e8
%D 2020
%X Enhancing 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:32445619
%R 10.1016/j.immuni.2020.05.001
%U https://inrepo02.dkfz.de/record/157001