Cancer Immunology, Immunotherapy

, Volume 58, Issue 1, pp 31–38

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

  • Daniele Santini
  • Federico Martini
  • Maria Elisabetta Fratto
  • Sara Galluzzo
  • Bruno Vincenzi
  • Chiara Agrati
  • Federica Turchi
  • Paola Piacentini
  • Laura Rocci
  • John S. Manavalan
  • Giuseppe Tonini
  • Fabrizio Poccia
Original Article

DOI: 10.1007/s00262-008-0521-6

Cite this article as:
Santini, D., Martini, F., Fratto, M.E. et al. Cancer Immunol Immunother (2009) 58: 31. doi:10.1007/s00262-008-0521-6

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.

Keywords

γδ T cells Zoledronic acid Bisphosphonates Cancer patients 

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

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Daniele Santini
    • 1
  • Federico Martini
    • 2
  • Maria Elisabetta Fratto
    • 1
  • Sara Galluzzo
    • 1
  • Bruno Vincenzi
    • 1
  • Chiara Agrati
    • 2
  • Federica Turchi
    • 2
  • Paola Piacentini
    • 2
  • Laura Rocci
    • 1
  • John S. Manavalan
    • 3
  • Giuseppe Tonini
    • 1
  • Fabrizio Poccia
    • 2
  1. 1.Medical OncologyUniversity Campus Bio-MedicoRomeItaly
  2. 2.National Institute for Infectious Diseases Lazzaro Spallanzani I.R.C.C.S.RomeItaly
  3. 3.Department of MedicineColumbia UniversityNew YorkUSA

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