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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume58
Issue number1
DOIs
Publication statusPublished - Jan 2009

Keywords

  • γδ T cells
  • Bisphosphonates
  • Cancer patients
  • Zoledronic acid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

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