1. The effects of systemic treatment with aminobisphosphonates and statins on circulating Vγ9Vδ2-T cells in patients with advanced cancer.
- Author
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Schneiders FL, Huijts CM, Reijm M, Bontkes HJ, Verheul HMW, de Gruijl TD, and van der Vliet HJ
- Subjects
- Acute-Phase Reaction etiology, Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Bone Density Conservation Agents adverse effects, Bone Neoplasms complications, Bone Neoplasms secondary, Breast Neoplasms complications, Breast Neoplasms pathology, Diphosphonates adverse effects, Diphosphonates chemistry, Female, Granzymes metabolism, HLA-DR Antigens metabolism, Humans, Immunophenotyping, Lymphocyte Activation drug effects, Male, Middle Aged, Perforin metabolism, Pilot Projects, Prostatic Neoplasms complications, Prostatic Neoplasms pathology, Receptors, Antigen, T-Cell, gamma-delta metabolism, Simvastatin adverse effects, Acute-Phase Reaction immunology, Antineoplastic Agents therapeutic use, Bone Density Conservation Agents therapeutic use, Bone Neoplasms drug therapy, Breast Neoplasms drug therapy, Diphosphonates therapeutic use, Drug-Related Side Effects and Adverse Reactions immunology, Prostatic Neoplasms drug therapy, Simvastatin therapeutic use, T-Lymphocytes physiology
- 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., (Copyright © 2017 Elsevier GmbH. All rights reserved.)
- Published
- 2018
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