title: Zoledronic acid-induced expansion of γδ T cells from early-stage breast cancer patients: effect of IL-18 on helper NK cells.
abstract: Human γδ 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 γδ T cells may contribute to this additive effect, the responsiveness of γδ T cells from early-stage breast cancer patients has not been fully investigated. In this study, we determined the number, frequency, and responsiveness of Vγ2Vδ2 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 Vγ2Vδ2 T cells from patients with low frequencies of Vγ2Vδ2 T cells was significantly diminished. IL-18, however, enhanced ex vivo proliferative responses of Vγ2Vδ2 T cells and helper NK cells from patients with either low or high frequencies of Vγ2Vδ2 T cells. Treatment of breast cancer patients with Zol alone decreased the number of Vγ2Vδ2 T cells and reduced their ex vivo responsiveness. These results demonstrate that Zol can elicit immunological responses by γδ T cells from early-stage breast cancer patients, but that frequent in vivo treatment reduces Vγ2Vδ2 T cell numbers and their responsiveness to stimulation.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Sugie
authors.forename: Kaoru
authors.initials: K
authors.lastname: Murata-Hirai
authors.forename: Masashi
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Craig T
authors.initials: CT
authors.lastname: Morita
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Minato
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D016219:Immunotherapy, Adoptive / Q000379:methods; D020382:Interleukin-18 / Q000276:immunology / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008875:Middle Aged; D009367:Neoplasm Staging; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D020382:Interleukin-18; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid