Abstract
Activation by zoledoronic acid and IL-18 of γδ T cells from early-stage breast cancer patients in the context of helper NK cells
Journal of clinical oncology, Vol.30(15_suppl), pp.e21004-e21004
05/20/2012
DOI: 10.1200/jco.2012.30.15_suppl.e21004
Abstract
e21004
Background: 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. Methods: Breast cancer patients (n=80) were enrolled after institutional review board approval and with written informed consent. Peripheral blood mononuclear cells (PBMC) were purified and stimulated with Zol/IL-2 or Zol/IL-2/IL-18 for 2 to 10 days. The expanded cells were assessed on flow cytometry and the production of IFN-γ and TNF-α measured through ELISA. Results: 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 Vγ2Vδ2T cells and helper NK cells (CD3
-
CD56
bright
CD11c
+
CD14
-
CD16
+
NKGD2
+
NKp44
low
) from patients with either low or high frequencies of Vγ2Vδ2 T cells. Cell-to-cell contact between γδ T and helper NK cells appeared to promote expansion of γδ T cells. Exogenous IL-18 markedly enhanced IFN-γ and TNF-α production from PBMC stimulated by Zol/IL-2, whereas the addition of an anti-IL-18Rα mAb reduced cytokine production. Conclusions: These results demonstrate that Zol elicits immunological responses by γδ T cells from early-stage breast cancer patients and IL-18 enhances proliferative responses and effector functions of γδ T cells in the context of helper NK cells.
Details
- Title: Subtitle
- Activation by zoledoronic acid and IL-18 of γδ T cells from early-stage breast cancer patients in the context of helper NK cells
- Creators
- Tomoharu Sugie - Kyoto UniversityKaoru Murata-Hirai - Kyoto UniversityMasashi Iwasaki - Kyoto UniversityCraig T Morita - University of IowaWen Li - Hyogo Medical UniversityHaruki Okamura - Hyogo Medical UniversityNagahiro Minato - Kyoto UniversityMasakazu Toi - Kyoto UniversityYoshimasa Tanaka - Kyoto University
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.30(15_suppl), pp.e21004-e21004
- DOI
- 10.1200/jco.2012.30.15_suppl.e21004
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2012
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984363297902771
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