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@ARTICLE{Hanna:178063,
author = {B. S. Hanna$^*$ and L. Llaó-Cid$^*$ and M. Iskar$^*$ and
P. M. Roessner$^*$ and L. C. Klett$^*$ and J. K. L. Wong$^*$
and Y. Paul$^*$ and N. Ioannou and S. Öztürk$^*$ and N.
Mack$^*$ and V. Kalter$^*$ and D. Colomer and E. Campo and
J. Bloehdorn and S. Stilgenbauer and S. Dietrich$^*$ and M.
Schmidt and R. Gabriel and K. Rippe$^*$ and M. Feuerer and
A. G. Ramsay and P. Lichter$^*$ and M. Zapatka$^*$ and M.
Seiffert$^*$},
title = {{I}nterleukin-10 receptor signaling promotes the
maintenance of a {PD}-1int {TCF}-1+ {CD}8+ {T} cell
population that sustains anti-tumor immunity.},
journal = {Immunity},
volume = {54},
number = {12},
issn = {1074-7613},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DKFZ-2021-03072},
pages = {2825-2841.e10},
year = {2021},
note = {#EA:B060#LA:B060# / 2021 Dec 14;54(12):2825-2841.e10},
abstract = {T cell exhaustion limits anti-tumor immunity and responses
to immunotherapy. Here, we explored the microenvironmental
signals regulating T cell exhaustion using a model of
chronic lymphocytic leukemia (CLL). Single-cell analyses
identified a subset of PD-1hi, functionally impaired CD8+
T cells that accumulated in secondary lymphoid organs
during disease progression and a functionally competent
PD-1int subset. Frequencies of PD-1int TCF-1+ CD8+ T cells
decreased upon Il10rb or Stat3 deletion, leading to
accumulation of PD-1hi cells and accelerated tumor
progression. Mechanistically, inhibition of IL-10R signaling
altered chromatin accessibility and disrupted cooperativity
between the transcription factors NFAT and AP-1, promoting a
distinct NFAT-associated program. Low IL10 expression or
loss of IL-10R-STAT3 signaling correlated with increased
frequencies of exhausted CD8+ T cells and poor survival in
CLL and in breast cancer patients. Thus, balance between
PD-1hi, exhausted CD8+ T cells and functional PD-1int
TCF-1+ CD8+ T cells is regulated by cell-intrinsic IL-10R
signaling, with implications for immunotherapy.},
keywords = {CD8(+) T cells (Other) / CLL (Other) / IL-10 (Other) /
IL-10R (Other) / NFAT (Other) / PD-1 heterogeneity (Other) /
STAT3 (Other) / T cell exhaustion (Other) / TCF-1 (Other) /
tumor microenvironment (Other)},
cin = {B060 / B066 / D100},
ddc = {610},
cid = {I:(DE-He78)B060-20160331 / I:(DE-He78)B066-20160331 /
I:(DE-He78)D100-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34879221},
doi = {10.1016/j.immuni.2021.11.004},
url = {https://inrepo02.dkfz.de/record/178063},
}