Immunome Research
Open Access
ISSN: 1745-7580
ISSN: 1745-7580
Tomoharu Suige1, Atif SMI1, Kaoru Murata-Hirai1, Masashi Iwasaki1, Craig T Morita2, Wen Li3, Haruki Okamura3, Nagahiro Minato1, Masakazu Toi1 and Yoshimasa Tanaka1
1Kyoto University, Japan 2University of Iowa, USA 3Hyogo College of Medicine, Japan
Posters-Accepted Abstracts: Immunome Res
Introduction: Human �³�´ 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 �³�´ T cells may contribute to this additive effect, the responsiveness of �³�´ T cells from early-stage breast cancer patients has not been fully investigated. Objective: In this study, we determined the number, frequency, and responsiveness of V�³2V�´2 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-�³ and TNF-�± measured through ELISA. Results: The responsiveness of V�³2V�´2 T cells from patients with low frequencies of V�³2V�´2 T cells was significantly diminished. IL-18, however, enhanced ex vivo proliferative responses of V�³2V�´2T cells and helper NK cells (CD3-CD56brightCD11c+CD14- CD16+NKGD2+NKp44low) from patients with either low or high frequencies of V�³2V�´2 T cells. Cell-to-cell contact between �³�´ T and helper NK cells appeared to promote expansion of �³�´ T cells. Exogenous IL-18 markedly enhanced IFN-�³ and TNF-�± production from PBMC stimulated by Zol/IL-2, whereas the addition of an anti-IL-18R�± mAb reduced cytokine production. Conclusion: These results demonstrate that Zol elicits immunological responses by �³�´ T cells from early-stage breast cancer patients and IL-18 enhances proliferative responses and effector functions of �³�´ T cells in the context of helper NK cells.
Email: atifokaz@gmail.com