TY  - JOUR
AU  - Ni, Jing
AU  - Wang, Xi
AU  - Stojanovic, Ana
AU  - Zhang, Qin
AU  - Wincher, Marian
AU  - Bühler, Lea Katharina
AU  - Arnold, Annette
AU  - Correia, Margareta P
AU  - Winkler, Manuel
AU  - Koch, Philipp-Sebastian
AU  - Sexl, Veronika
AU  - Höfer, Thomas
AU  - Cerwenka, Adelheid
TI  - Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity.
JO  - Immunity
VL  - 52
IS  - 6
SN  - 1074-7613
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2020-01298
SP  - 1075 - 1087.e8
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:32445619
DO  - DOI:10.1016/j.immuni.2020.05.001
UR  - https://inrepo02.dkfz.de/record/157001
ER  -