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

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

Tomoharu Sugie, Kaoru Murata-Hirai, Masashi Iwasaki, Craig Morita, Wen Li, Haruki Okamura, Nagahiro Minato, Masakazu Toi and Yoshimasa Tanaka
Cancer Immunology, Immunotherapy, Vol.62(4), pp.677-687
04/2013
DOI: 10.1007/s00262-012-1368-4
PMCID: PMC3639312
PMID: 23151944
url
https://www.ncbi.nlm.nih.gov/pmc/articles/3639312View
Open Access

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.
Breast Cancer Immunology Oncology Phosphoantigen γδ T cells Medicine & Public Health IL-18 Cancer Research N-BP Helper NK cells

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