Zoledronic acid-induced expansion of ?? T cells from early-stage breast cancer patients: effect of IL-18 on helper NK cells.

ABSTRACT: Human ?? T cells display potent cytotoxicity against various tumor cells pretreated with zoledronic acid (Zol). Zol has shown benefits when added to adjuvant endocrine therapy for patients with early-stage breast cancer or to standard chemotherapy for patients with multiple myeloma. Although ?? T cells may contribute to this additive effect, the responsiveness of ?? T cells from early-stage breast cancer patients has not been fully investigated. In this study, we determined the number, frequency, and responsiveness of V?2V?2 T cells from early- and late-stage breast cancer patients and examined the effect of IL-18 on their ex vivo expansion. The responsiveness of V?2V?2 T cells from patients with low frequencies of V?2V?2 T cells was significantly diminished. IL-18, however, enhanced ex vivo proliferative responses of V?2V?2 T cells and helper NK cells from patients with either low or high frequencies of V?2V?2 T cells. Treatment of breast cancer patients with Zol alone decreased the number of V?2V?2 T cells and reduced their ex vivo responsiveness. These results demonstrate that Zol can elicit immunological responses by ?? T cells from early-stage breast cancer patients, but that frequent in vivo treatment reduces V?2V?2 T cell numbers and their responsiveness to stimulation.

SUBMITTER: Sugie T 

PROVIDER: S-EPMC3639312 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature