In vivo effects of zoledronic acid on peripheral gammadelta T lymphocytes in early breast cancer patients.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Santini
Daniele
D
Medical Oncology, University Campus Bio-Medico, Rome, Italy.
Martini
Federico
F
Fratto
Maria Elisabetta
ME
Galluzzo
Sara
S
Vincenzi
Bruno
B
Agrati
Chiara
C
Turchi
Federica
F
Piacentini
Paola
P
Rocci
Laura
L
Manavalan
John S
JS
Tonini
Giuseppe
G
Poccia
Fabrizio
F
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D016131:Lymphocyte Subsets / Q000187:drug effects; D008875:Middle Aged; D009367:Neoplasm Staging; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000077211:Zoledronic Acid