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Tumor-derived exosomes modulate PD-L1 expression in monocytes.
- Source :
- Science Immunology; 2017, Vol. 2 Issue 13, p1-11, 11p, 6 Graphs
- Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 24709468
- Volume :
- 2
- Issue :
- 13
- Database :
- Complementary Index
- Journal :
- Science Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 164972028
- Full Text :
- https://doi.org/10.1126/sciimmunol.aah5509