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01-04-2013 | Original article

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

Authors: Tomoharu Sugie, Kaoru Murata-Hirai, Masashi Iwasaki, Craig T. Morita, Wen Li, Haruki Okamura, Nagahiro Minato, Masakazu Toi, Yoshimasa Tanaka

Published in: Cancer Immunology, Immunotherapy | Issue 4/2013

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.

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Title: Zoledronic acid-induced expansion of γδ T cells from early-stage breast cancer patients: effect of IL-18 on helper NK cells
Authors: Tomoharu Sugie
Kaoru Murata-Hirai
Masashi Iwasaki
Craig T. Morita
Wen Li
Haruki Okamura
Nagahiro Minato
Masakazu Toi
Yoshimasa Tanaka
Publication date: 01-04-2013
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 4/2013
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-012-1368-4

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