Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8472069 | Immunobiology | 2018 | 7 Pages |
Abstract
Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro. We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment.
Keywords
TNFαHMBPPNCI-CTCNaN3PerCPNBPIMDMIFNγPAGAPCIPPPBSFPPFITCPBMCBSAbovine serum albuminallophycocyaninaminobisphosphonatesAprStatinsIscove’s Modified Dulbecco’s Mediumisopentenyl pyrophosphatetumor necrosis factor alphaperipheral blood mononuclear cellsfarnesyl diphosphatephycoerythrinPhosphate buffered salinefluorescein isothiocyanateAntigenacute phase responseperidinin chlorophyll proteinInterferon gamma
Related Topics
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Biochemistry, Genetics and Molecular Biology
Cell Biology
Authors
Famke L. Schneiders, Charlotte M. Huijts, Martine Reijm, Hetty J. Bontkes, Henk M.W. Verheul, Tanja D. de Gruijl, Hans J. van der Vliet,