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In vivo effects of zoledronic acid on peripheral γδ T lymphocytes in early breast cancer patients

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Abstract

Introduction

Amino-bisphosphonates are potent activators of human γδ T cells. The aim of our study was to evaluate the immunomodulating properties of a single-dose of zoledronic acid (ZA) on γδ T cells in a select group of disease-free breast cancer patients with osteopenia.

Materials and methods

Blood samples were obtained, from 23 patients, before and 7, 28, 56, 90 and 180 days after a single-dose (4 mg) of ZA and analyzed by flow cyometry.

Results

A significant decrease of the different γδ T cell subsets was observed: Naïve (CD3+/Vdelta2+/CD45RA+/CD27+) after 180 days (P < 0.01); Central Memory (CD3+/Vdelta2+/CD45RA-CD27+) after 28 (P < 0.05), 90 (P < 0.01) and 180 days (P < 0.01); and Effector Memory (CD3+/Vdelta2+/CD45RA-/CD27-) after 56 (P < 0.01) and 90 (P < 0.05) days. Based on the observed γδ T cells kinetics patients could be divided in two groups: “responders” that showed a significant decrease in total numbers of γδ T cells and “non-responders” that showed no significant change. However, in vitro phosphoantigen stimulation of patients cells did not show significant differences in terms of IFN-γ response by Vδ2 T cells.

Conclusion

We describe for the first time a long-lasting activation of effector subsets of γδ T cells in disease-free breast cancer patients after a single-dose of ZA. Our results highlight the need to further investigate the clinical significance of the immunomodulating properties of N-BPs.

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Abbreviations

N-BPs:

Amino-bisphosphonates

BPs:

Bisphosphonates

ZA:

Zoledronic acid

γ/δ T Ly:

γ/δ T lymphocytes

IPP:

Isopentenyl-diphosphate

CM:

Central memory

EM:

Effector memory

TE:

Terminal effectors

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Acknowledgments

This work is in memory of Fabrizio Poccia. This work was supported by grants from MIUR (COFIN, 2005) and from “Giuliana Cardarelli Mazzi” cancer research foundation. Any financial/commercial conflicts have been disclosed.

Conflict of interest statement

The authors declare no financial or commercial conflicts of interest.

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Authors and Affiliations

  1. Medical Oncology, University Campus Bio-Medico, 00155, Rome, Italy

    Daniele Santini, Maria Elisabetta Fratto, Sara Galluzzo, Bruno Vincenzi, Laura Rocci & Giuseppe Tonini

  2. National Institute for Infectious Diseases Lazzaro Spallanzani I.R.C.C.S., Rome, Italy

    Federico Martini, Chiara Agrati, Federica Turchi, Paola Piacentini & Fabrizio Poccia

  3. Department of Medicine, Columbia University, New York, USA

    John S. Manavalan

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  1. Daniele Santini
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  2. Federico Martini
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Correspondence to Giuseppe Tonini.

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Santini, D., Martini, F., Fratto, M.E. et al. In vivo effects of zoledronic acid on peripheral γδ T lymphocytes in early breast cancer patients. Cancer Immunol Immunother 58, 31–38 (2009). https://doi.org/10.1007/s00262-008-0521-6

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  • DOI: https://doi.org/10.1007/s00262-008-0521-6

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