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DOI | 10.1126/science.aas9090 |
NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination | |
Ruscetti, Marcus1; Leibold, Josef1; Bott, Matthew J.1; Fennell, Myles1; Kulick, Amanda2; Salgado, Nelson R.1; Chen, Chi-Chao1; Ho, Yu-jui1; Sanchez-Rivera, Francisco J.1; Fencht, Judith3; Baslan, Timour1; Tian, Sha1; Chen, Hsuan-An1; Romesser, Paul B.1; Poirier, John T.2,4; Rudin, Charles M.2,4; de Stanchina, Elisa2; Manchado, Eusebio1; Sherr, Charles J.5,6; Lowe, Scott W.1,6 | |
2018-12-21 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6421页码:1416-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Molecularly targeted therapies aim to obstruct cell autonomous programs required for tumor growth. We show that mitogen-activated protein kinase (MARK) and cyclin-dependent kinase 4/6 inhibitors act in combination to suppress the proliferation of KRAS-mutant lung cancer cells while simultaneously provoking a natural killer (NK) cell surveillance program leading to tumor cell death. The drug combination, but neither agent alone, promotes retinoblastoma (RB) protein-mediated cellular senescence and activation of the irnmunomodulatory senescence-associated secretory phenotype (SASP). SASP components tumor necrosis factor-u and intercellular adhesion molecule-1 are required for NK cell surveillance of drug-treated tumor cells, which contributes to tumor regressions and prolonged survival in a KRAS-mutant lung cancer mouse model. Therefore, molecularly targeted agents capable of inducing senescence can produce tumor control through non-cell autonomous mechanisms involving NK cell surveillance. |
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:000453845000062 |
WOS关键词 | SECRETORY PHENOTYPE ; ANTITUMOR-ACTIVITY ; T-CELL ; SENESCENCE ; CANCER ; INHIBITION ; EXPRESSION ; P53 ; SURVEILLANCE ; ACTIVATION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
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/200378 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, Sloan Kettering Inst, New York, NY 10065 USA; 2.Mem Sloan Kettering Canc Ctr, Dept Mol Pharmacol, Sloan Kettering Inst, New York, NY 10065 USA; 3.Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, New York, NY 10065 USA; 4.Mem Sloan Kettering Canc Ctr, Immunol Program, New York, NY 10065 USA; 5.Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA; 6.St Jude Childrens Res Hosp, Dept Tumor Cell Biol, 332 N Lauderdale St, Memphis, TN 38105 USA |
推荐引用方式 GB/T 7714 | Ruscetti, Marcus,Leibold, Josef,Bott, Matthew J.,et al. NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination[J]. SCIENCE,2018,362(6421):1416-+. |
APA | Ruscetti, Marcus.,Leibold, Josef.,Bott, Matthew J..,Fennell, Myles.,Kulick, Amanda.,...&Lowe, Scott W..(2018).NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination.SCIENCE,362(6421),1416-+. |
MLA | Ruscetti, Marcus,et al."NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination".SCIENCE 362.6421(2018):1416-+. |
条目包含的文件 | 条目无相关文件。 |
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