Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 71, Issue 12, Pages 2335-2346Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-013-1495-x
Keywords
Nitrogen-bisphosphonates; Osteoporosis therapy; Adverse drug effects; gamma delta T cells; Cancer therapy
Categories
Funding
- Alexander von Humboldt Foundation of Germany
- Faculty of Medicine Grant from Christian-Albrechts University of Kiel
- Deutsche Forschungsgemeinschaft [Ka 502/10-2]
Ask authors/readers for more resources
Nitrogen-bisphosphonates (n-BP), such as zoledronate, are the main class of drugs used for the prevention of osteoporotic fractures and the management of cancer-associated bone disease. However, long-term or high-dose use has been associated with certain adverse drug effects, such as osteonecrosis of the jaw and the loss of peripheral of blood V gamma 9V delta 2 T cells, which appear to be linked to drug-induced 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 V gamma 9V delta 2 T cells. Furthermore, we found this zoledronate-mediated inhibition by neutrophils could be overcome to fully reconstitute V gamma 9V delta 2 T cell proliferation by concomitantly targeting neutrophil-derived 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 n-BP treatment on immune homeostasis and to improve the success of immunotherapy trials based on harnessing the anticancer potential of peripheral blood gamma delta T cells in the context of n-BP treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available