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Gamma delta T cells kill myeloma cells by sensing mevalonate metabolites and ICAM-1 molecules on cell surface |
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| Authors: | Uchida Ryo Ashihara Eishi Sato Kiyoshi Kimura Shinya Kuroda Junya Takeuchi Miki Kawata Eri Taniguchi Kyoko Okamoto Masashi Shimura Kazuho Kiyono Yasushi Shimazaki Chihiro Taniwaki Masafumi Maekawa Taira |
| Institution: | a Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan b Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan c Radioisotopes Research Laboratory, Kyoto University Hospital, Kyoto, Japan |
| Abstract: | We evaluated the mechanism of recognition of myeloma cells by γδT cells. The expanded γδT cells killed RPMI8226 and U266 myeloma cells in a γδT-cell dose-dependent manner. Pretreatment of myeloma cells with zoledronic acid or mevastatin showed that γδT cells kill myeloma cells by recognizing the mevalonate metabolites. The expression level of intercellular cell adhesion molecule-1 (ICAM-1) on myeloma cells correlates with the cytotoxicity by γδT cells. Pretreatment of RPMI8226 and U266 with an anti-ICAM-1 monoclonal antibody inhibited their cytolysis. Moreover, AMO-1 myeloma cells transfected with of human ICAM-1 cDNA were susceptible to γδT cells compared to parental AMO-1 cells. In conclusion, γδT cells recognize the mevalonate metabolites and ICAM-1 on myeloma cells. |
| Keywords: | Immunotherapy Multiple myeloma γδT cells ICAM-1 Bisphosphonate |
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