Authors: Shirin Kalyan Vijayanand Chandrasekaran Elgar S Quabius Thisbe K Lindhorst Dieter Kabelitz
Publish Date: 2013/10/26
Volume: 71, Issue: 12, Pages: 2335-2346
Abstract
Nitrogenbisphosphonates nBP such as zoledronate are the main class of drugs used for the prevention of osteoporotic fractures and the management of cancerassociated bone disease However longterm or highdose use has been associated with certain adverse drug effects such as osteonecrosis of the jaw and the loss of peripheral of blood Vγ9Vδ2 T cells which appear to be linked to druginduced immune dysfunction In this report we show that neutrophils present in human peripheral blood readily take up zoledronate and this phenomenon is associated with the potent immune suppression of human peripheral blood Vγ9Vδ2 T cells Furthermore we found this zoledronatemediated inhibition by neutrophils could be overcome to fully reconstitute Vγ9Vδ2 T cell proliferation by concomitantly targeting neutrophilderived hydrogen peroxide serine proteases and arginase I activity These findings will enable the development of targeted strategies to mitigate some of the adverse effects of nBP treatment on immune homeostasis and to improve the success of immunotherapy trials based on harnessing the anticancer potential of peripheral blood γδ T cells in the context of nBP treatmentSK was supported by a Fellowship from the Alexander von Humboldt Foundation of Germany and a Faculty of Medicine Grant from ChristianAlbrechts University of Kiel DK acknowledges grant support from the Deutsche Forschungsgemeinschaft Ka 502/102 and “InflammationatInterfaces” Cluster of Excellence We would like to thank Hilke Clasen Department of Immunology for technical assistance and Dr Millan Patel University of British Columbia for review of the manuscript
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