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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.

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.
AuthorsTomoharu Sugie, Kaoru Murata-Hirai, Masashi Iwasaki, Craig T Morita, Wen Li, Haruki Okamura, Nagahiro Minato, Masakazu Toi, Yoshimasa Tanaka
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 62 Issue 4 Pg. 677-87 (Apr 2013) ISSN: 1432-0851 [Electronic] Germany
PMID23151944 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Diphosphonates
  • Imidazoles
  • Interleukin-18
  • Receptors, Antigen, T-Cell, gamma-delta
  • Zoledronic Acid
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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