Atif S M I1, Tomoharu Suige2, Kaoru Murata-Hirai2, Masashi Iwasaki2, Craig T Morita3, Wen Li4, Haruki Okamura4, Nagahiro Minato2, Masakazu Toi2 and Yoshimasa Tanaka2
1Alneelain University, Sudan 2Kyoto University, Japan 3University of Iowa, USA 4Hyogo College of Medicine, Japan
Posters-Accepted Abstracts: J Clin Cell Immunol
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 latestage 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-CD56 bright CD11c+CD14-CD16+NKGD2+NKp44 low) 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 demonstrated 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.
Atif SM Idrees has completed his PhD from Kyoto University School of Medicine, Kyoto, Japan. He is now the coordinator of educational media development at the Faculty of Science and Technology, Alneelain University, Khartoum, Sudan. He has been involved in many research activities beside serving as an advisor for undergraduate and postgraduate research projects. He is also available internationally through his collaboration with research institutes in more than country. His main research interest is in the field of Immunology, especially Cancer Immunology and Immunotherapy.
Email: atifokaz@gmail.com
