Inhibition of NK Reactivity Against Solid Tumors by Platelet-Derived RANKL.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_7F88D734665E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inhibition of NK Reactivity Against Solid Tumors by Platelet-Derived RANKL.
Journal
Cancers
Author(s)
Clar K.L., Hinterleitner C., Schneider P., Salih H.R., Maurer S.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
26/02/2019
Peer-reviewed
Oui
Volume
11
Number
3
Language
english
Abstract
NK cells play an important role in tumor immunosurveillance. Their reactivity is governed by various activating and inhibitory surface receptors, which include several members of the TNF/TNF receptor family. For more than 50 years, it has been recognized that tumor immunosurveillance and in particular NK cell antitumor reactivity is largely influenced by platelets, but the underlying mechanisms remain to be fully elucidated. Here we report that upon activation, which reportedly occurs following interaction with cancer cells, platelets upregulate the TNF family member RANKL. Comparative analysis of the expression of RANK among different NK cell subsets and RANKL on platelets in cancer patients and healthy volunteers revealed a distinct malignant phenotype, and platelet-derived RANKL was found to inhibit the activity of normal NK cells against cancer cells. Notably, NK cell antitumor reactivity could be partially restored by application of denosumab, a RANKL-neutralizing antibody approved for treatment of benign and malignant osteolysis. Together, our data not only unravel a novel mechanism of tumor immune evasion mediated by platelets, but they also provide a functional explanation for the clinical observation that denosumab, beyond protecting from bone loss, may prolong disease-free survival in patients with solid tumors.
Keywords
NK cells, RANK/RANKL, cancer, denosumab, immune evasion, metastasis, platelets
Pubmed
Web of science
Open Access
Yes
Create date
07/04/2019 14:34
Last modification date
20/08/2019 14:40
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