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@ARTICLE{Ni:157001,
author = {J. Ni$^*$ and X. Wang$^*$ and A. Stojanovic$^*$ and Q.
Zhang$^*$ and M. Wincher and L. K. Bühler$^*$ and A.
Arnold$^*$ and M. P. Correia$^*$ and M. Winkler and P.-S.
Koch and V. Sexl and T. Höfer$^*$ and A. Cerwenka$^*$},
title = {{S}ingle-{C}ell {RNA} {S}equencing of
{T}umor-{I}nfiltrating {NK} {C}ells {R}eveals that
{I}nhibition of {T}ranscription {F}actor {HIF}-1α
{U}nleashes {NK} {C}ell {A}ctivity.},
journal = {Immunity},
volume = {52},
number = {6},
issn = {1074-7613},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2020-01298},
pages = {1075 - 1087.e8},
year = {2020},
abstract = {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.},
cin = {B086 / D080},
ddc = {610},
cid = {I:(DE-He78)B086-20160331 / I:(DE-He78)D080-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32445619},
doi = {10.1016/j.immuni.2020.05.001},
url = {https://inrepo02.dkfz.de/record/157001},
}