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@ARTICLE{Haderk:125347,
author = {F. Haderk$^*$ and R. Schulz$^*$ and M. Iskar$^*$ and L. L.
Cid$^*$ and T. Worst$^*$ and K. V. Willmund$^*$ and A.
Schulz$^*$ and U. Warnken$^*$ and J. Seiler$^*$ and A.
Benner$^*$ and M. Nessling$^*$ and T. Zenz$^*$ and M. Göbel
and J. Dürig and S. Diederichs$^*$ and J. Paggetti and E.
Moussay and S. Stilgenbauer and M. Zapatka$^*$ and P.
Lichter$^*$ and M. Seiffert},
title = {{T}umor-derived exosomes modulate {PD}-{L}1 expression in
monocytes.},
journal = {Science immunology},
volume = {2},
number = {13},
issn = {2470-9468},
address = {Washington, DC},
publisher = {AAAS},
reportid = {DKFZ-2017-01480},
pages = {eaah5509 -},
year = {2017},
note = {Science Immunology (Sci. Immunol.) = 2470-9468 (import from
CrossRef, PubMed, )},
abstract = {In chronic lymphocytic leukemia (CLL), monocytes and
macrophages are skewed toward protumorigenic phenotypes,
including the release of tumor-supportive cytokines and the
expression of immunosuppressive molecules such as programmed
cell death 1 ligand 1 (PD-L1). To understand the mechanism
driving protumorigenic skewing in CLL, we evaluated the role
of tumor cell-derived exosomes in the cross-talk with
monocytes. We carried out RNA sequencing and proteome
analyses of CLL-derived exosomes and identified noncoding Y
RNA hY4 as a highly abundant RNA species that is enriched in
exosomes from plasma of CLL patients compared with healthy
donor samples. Transfer of CLL-derived exosomes or hY4 alone
to monocytes resulted in key CLL-associated phenotypes,
including the release of cytokines, such as C-C motif
chemokine ligand 2 (CCL2), CCL4, and interleukin-6, and the
expression of PD-L1. These responses were abolished in
Toll-like receptor 7 (TLR7)-deficient monocytes, suggesting
exosomal hY4 as a driver of TLR7 signaling. Pharmacologic
inhibition of endosomal TLR signaling resulted in a
substantially reduced activation of monocytes in vitro and
attenuated CLL development in vivo. Our results indicate
that exosome-mediated transfer of noncoding RNAs to
monocytes contributes to cancer-related inflammation and
concurrent immune escape via PD-L1 expression.},
cin = {B060 / B110 / C060 / B150 / W230 / G100 / L601 / B100 /
G250},
ddc = {610},
cid = {I:(DE-He78)B060-20160331 / I:(DE-He78)B110-20160331 /
I:(DE-He78)C060-20160331 / I:(DE-He78)B150-20160331 /
I:(DE-He78)W230-20160331 / I:(DE-He78)G100-20160331 /
I:(DE-He78)L601-20160331 / I:(DE-He78)B100-20160331 /
I:(DE-He78)G250-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28754746},
doi = {10.1126/sciimmunol.aah5509},
url = {https://inrepo02.dkfz.de/record/125347},
}