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| 001 | 125347 | ||
| 005 | 20240228145524.0 | ||
| 024 | 7 | _ | |a 10.1126/sciimmunol.aah5509 |2 doi |
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| 041 | _ | _ | |a eng |
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| 100 | 1 | _ | |a Haderk, Franziska |0 0000-0001-9658-2778 |b 0 |e First author |
| 245 | _ | _ | |a Tumor-derived exosomes modulate PD-L1 expression in monocytes. |
| 260 | _ | _ | |a Washington, DC |c 2017 |b AAAS |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a Science Immunology (Sci. Immunol.) = 2470-9468 (import from CrossRef, PubMed, ) |
| 520 | _ | _ | |a 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. |
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| 700 | 1 | _ | |a Schulz, Ralph |0 0000-0002-8594-2050 |b 1 |
| 700 | 1 | _ | |a Iskar, Murat |0 0000-0001-8603-4313 |b 2 |
| 700 | 1 | _ | |a Cid, Laura Llaó |0 0000-0003-0543-6084 |b 3 |
| 700 | 1 | _ | |a Worst, Thomas |0 0000-0001-5429-126X |b 4 |
| 700 | 1 | _ | |a Willmund, Karolin V |0 0000-0002-2935-107X |b 5 |
| 700 | 1 | _ | |a Schulz, Angela |0 0000-0002-4491-1581 |b 6 |
| 700 | 1 | _ | |a Warnken, Uwe |0 0000-0001-9337-1879 |b 7 |
| 700 | 1 | _ | |a Seiler, Jana |0 0000-0002-7633-6278 |b 8 |
| 700 | 1 | _ | |a Benner, Axel |0 0000-0002-7238-6956 |b 9 |
| 700 | 1 | _ | |a Nessling, Michelle |0 0000-0002-0663-4026 |b 10 |
| 700 | 1 | _ | |a Zenz, Thorsten |0 0000-0001-7890-9845 |b 11 |
| 700 | 1 | _ | |a Göbel, Maria |b 12 |
| 700 | 1 | _ | |a Dürig, Jan |b 13 |
| 700 | 1 | _ | |a Diederichs, Sven |0 0000-0001-7901-4752 |b 14 |
| 700 | 1 | _ | |a Paggetti, Jérôme |0 0000-0001-9460-5876 |b 15 |
| 700 | 1 | _ | |a Moussay, Etienne |0 0000-0002-0879-8067 |b 16 |
| 700 | 1 | _ | |a Stilgenbauer, Stephan |b 17 |
| 700 | 1 | _ | |a Zapatka, Marc |0 0000-0001-8287-5967 |b 18 |
| 700 | 1 | _ | |a Lichter, Peter |0 0000-0002-2960-5279 |b 19 |
| 700 | 1 | _ | |a Seiffert, Martina |0 0000-0001-5155-663X |b 20 |e Last author |
| 773 | _ | _ | |a 10.1126/sciimmunol.aah5509 |g Vol. 2, no. 13, p. eaah5509 - |0 PERI:(DE-600)2862556-0 |n 13 |p eaah5509 - |t Science immunology |v 2 |y 2017 |x 2470-9468 |
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