Cytotoxic human peripheral blood-derived γδT cells kill glioblastoma cell lines: implications for cell-based immunotherapy for patients with glioblastoma.

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.;博士(医学)・甲第635号・平成27年5月28日;© Springer Verlag. The definitive version is available at " http://dx.doi.org/10.1007/s11060-013-1258-4 ";開始ページ : 31;終了ページ : 39;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/24062140

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書名 Cytotoxic human peripheral blood-derived γδT cells kill glioblastoma cell lines: implications for cell-based immunotherapy for patients with glioblastoma.
著作者等 Hironaka, Yasuo
Marutani, Akiko
Matsuda, Ryosuke
Motoyama, Yasushi
Nakagawa, Ichiro
Nakamura, Mitsutoshi
Nakase, Hiroyuki
Nishimura, Fumihiko
Ouji, Noriko
Ouji, Yukiteru
Park, Young Soo
Sugimoto, Tadashi
Takeshima, Yasuhiro
Tamura, Kentaro
Tsujimura, Takahiro
Yamada, Shuichi
Yoshikawa, Masahide
Nakazawa, Tsutomu
書名別名 ヒト細胞傷害性γδT細胞は膠芽腫細胞株を殺傷する:膠芽腫患者に対する免疫細胞治療の意義
出版元 Springer US
刊行年月 1983-
ページ数 v.
大きさ 26 cm
ISSN 0167594X
NCID AA10633712
AA1211769X
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言語 英語
出版国 アメリカ合衆国
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