In Vivo Effects of Zoledronic Acid on Peripheral Gammadelta T Lymphocytes in Early Breast Cancer Patients

Cancer Immunol Immunother. 2009 Jan;58(1):31-8. doi: 10.1007/s00262-008-0521-6. Epub 2008 May 6.

Abstract

Introduction: Amino-bisphosphonates are potent activators of human gammadelta T cells. The aim of our study was to evaluate the immunomodulating properties of a single-dose of zoledronic acid (ZA) on gammadelta 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 gammadelta 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 gammadelta T cells kinetics patients could be divided in two groups: "responders" that showed a significant decrease in total numbers of gammadelta 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-gamma response by Vdelta2 T cells.

Conclusion: We describe for the first time a long-lasting activation of effector subsets of gammadelta 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Diphosphonates / therapeutic use*
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Lymphocyte Subsets / drug effects
  • Middle Aged
  • Neoplasm Staging
  • Receptors, Antigen, T-Cell, alpha-beta / drug effects*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Zoledronic Acid

Substances

  • Antineoplastic Agents
  • Diphosphonates
  • Imidazoles
  • Receptors, Antigen, T-Cell, alpha-beta
  • Zoledronic Acid