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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Authors | Tomoharu Sugie, Kaoru Murata-Hirai, Masashi Iwasaki, Craig T Morita, Wen Li, Haruki Okamura, Nagahiro Minato, Masakazu Toi, Yoshimasa Tanaka |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 62
Issue 4
Pg. 677-87
(Apr 2013)
ISSN: 1432-0851 [Electronic] Germany |
PMID | 23151944
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Diphosphonates
- Imidazoles
- Interleukin-18
- Receptors, Antigen, T-Cell, gamma-delta
- Zoledronic Acid
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Topics |
- Breast Neoplasms
(drug therapy, immunology, pathology, therapy)
- Clinical Trials as Topic
- Combined Modality Therapy
- Diphosphonates
(therapeutic use)
- Female
- Humans
- Imidazoles
(therapeutic use)
- Immunotherapy, Adoptive
(methods)
- Interleukin-18
(immunology, therapeutic use)
- Killer Cells, Natural
(drug effects, immunology)
- Leukocytes, Mononuclear
(immunology)
- Middle Aged
- Neoplasm Staging
- Receptors, Antigen, T-Cell, gamma-delta
(biosynthesis, immunology)
- T-Lymphocytes, Helper-Inducer
(drug effects, immunology)
- Zoledronic Acid
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