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DOI | 10.1126/science.aao0505 |
Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity | |
de Andrade, Lucas Ferrari1,2; Tay, Rong En1,2; Pan, Deng1,2; Luoma, Adrienne M.1,2; Ito, Yoshinaga1,2; Badrinath, Soumya1,2; Tsoucas, Daphne3; Franz, Bettina1,2; May, Kenneth F., Jr.4; Harvey, Christopher J.1; Kobold, Sebastian1; Pyrdol, Jason W.1; Yoon, Charles4,5; Yuan, Guo-Cheng3; Hodi, F. Stephen4; Dranoff, Glenn4,6; Wucherpfennig, Kai W.1,2 | |
2018-03-30 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 359期号:6383页码:1537-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA alpha 3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and reduced human melanoma metastases in a humanized mouse model. Antitumor immunity was mediated mainly by natural killer (NK) cells through activation of NKG2D and CD16 Fc receptors. This approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000428657000049 |
WOS关键词 | I-RELATED CHAIN ; NKG2D RECEPTOR ; T-CELLS ; CUTTING EDGE ; LIGANDS ; EXPRESSION ; ACTIVATION ; CANCER ; CYTOTOXICITY ; MOLECULES |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/198304 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Dana Farber Canc Inst, Dept Canc Immunol & Virol, 450 Brookline Ave, Boston, MA 02215 USA; 2.Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA; 3.Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA; 4.Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA; 5.Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA; 6.Novartis Inst BioMed Res, 250 Massachusetts Ave, Cambridge, MA 02139 USA |
推荐引用方式 GB/T 7714 | de Andrade, Lucas Ferrari,Tay, Rong En,Pan, Deng,et al. Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity[J]. SCIENCE,2018,359(6383):1537-+. |
APA | de Andrade, Lucas Ferrari.,Tay, Rong En.,Pan, Deng.,Luoma, Adrienne M..,Ito, Yoshinaga.,...&Wucherpfennig, Kai W..(2018).Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity.SCIENCE,359(6383),1537-+. |
MLA | de Andrade, Lucas Ferrari,et al."Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity".SCIENCE 359.6383(2018):1537-+. |
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