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题目:: Cytotoxic human peripheral blood-derived γδT cells kill glioblastoma cell lines: implications for cell-based immunotherapy for patients with glioblastoma.
作者:: Nakazawa(Tsutomu),Nakamura(Mitsutoshi),Park(Young Soo),Motoyama(Yasushi),Hironaka(Yasuo),Nishimura(Fumihiko),Nakagawa(Ichiro),Yamada(Shuichi),Matsuda(Ryosuke),Tamura(Kentaro),Sugimoto(Tadashi),Takeshima(Yasuhiro),Marutani(Akiko),Tsujimura(Takahiro),Ouji(Noriko),Ouji(Yukiteru),Yoshikawa(Masahide),Nakase(Hiroyuki)
状态:: 发布时间2013-12-24 , 更新时间 2014-11-20
期刊:: J Neurooncol
摘要:: Glioblastoma (GBM) is a highly aggressive brain tumor for which novel therapeutic approaches, such as immunotherapy, are urgently needed. Zoledronate (ZOL), an inhibitor of osteoclastic activity, is known to stimulate peripheral blood-derived γδT cells and sensitize tumors to γδT cell-mediated killing. To investigate the feasibility of γδT cell-based immunotherapy for patients with GBM, we focused on the killing of GBM cell lines by γδT cells and the molecular mechanisms involved in these cell-cell interactions. Peripheral blood mononuclear cells were expanded in ZOL and interleukin (IL)-2 for 14 days, and γδT cells were enriched in the expanded cells by the immunomagnetic depletion of αβT cells. Gliomas are resistant to NK cells but susceptible to lymphokine-activated killer cells and some cytotoxic T lymphocytes. When the γδT cell-mediated killing of three GBM cell lines (U87MG, U138MG and A172 cells) and an NK-sensitive leukemia cell line (K562 cells) were tested, 32% U87MG, 15% U138MG, 1% A172, and 50% K562 cells were killed at an effector:target ratio of 5:1. The γδT cell-mediated killing of all three GBM cell lines was significantly enhanced by ZOL and this ZOL-enhanced killing was blocked by an anti-T cell receptor (TcR) antibody. These results indicated that TcR γδ is crucial for the recognition of ZOL-treated GBM cells by γδT cells. Since the low level killing of GBM cells by the γδT cells was enhanced by ZOL, γδT cell-targeting therapy in combination with ZOL treatment could be effective for patients with GBM.
语言:: eng
DOI:: 10.1007/s11060-013-1258-4

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