Research ArticleCANCER

Tumor-derived exosomes modulate PD-L1 expression in monocytes

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Science Immunology  28 Jul 2017:
Vol. 2, Issue 13, eaah5509
DOI: 10.1126/sciimmunol.aah5509

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Messaging with RNAs

Understanding interactions between tumor cells and immune cells is essential for tailoring immunocentric therapies to tumors. Here, Haderk et al. have identified a key role for tumor-derived exosomes in modulating immune responses to chronic lymphocytic leukemia (CLL). They report that CLL-derived exosomal RNAs promote monocytes in CLL patients to adopt an immunosuppressive phenotype, including promoting expression of PD-L1. They identify noncoding RNA hY4 as a key functional component of CLL-derived exosomes and show that hY4 promotes exosome-dependent skewing of monocytes in a TLR7-dependent manner. Using mouse models, they found that inhibition of TLR7 delayed progression of CLL, opening up the possibility that the TLR7 pathway could be therapeutically targeted in CLL.