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

Cancers
Kim L ClarStefanie Maurer

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, be...Continue Reading

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Citations

Jan 30, 2020·International Journal of Molecular Sciences·Maria Valeria CataniValeria Gasperi
May 29, 2020·Biomarkers in Medicine·Tanya N Augustine
Sep 11, 2019·Current Oncology Reports·Miriam Santiago KimpoShawn Lee
Mar 3, 2020·Frontiers in Immunology·Stefanie MaurerKorbinian N Kropp
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Jan 12, 2021·Frontiers in Immunology·Stefanie Maurer, Lucas Ferrari de Andrade
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Jun 3, 2021·Cancers·Martina HinterleitnerClemens Hinterleitner
Jul 3, 2021·Diagnostics·Yanjun ZhouStefanie Maurer

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Methods Mentioned

BETA
ELISA
density
FCS
FACS

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