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DOI | 10.1126/science.aar3593 |
Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy | |
Cristescu, Razvan1; Mogg, Robin1,6; Ayers, Mark1; Albright, Andrew1; Murphy, Erin1; Yearley, Jennifer1; Sher, Xinwei1; Liu, Xiao Qiao1; Lu, Hongchao1; Nebozhyn, Michael1; Zhang, Chunsheng1; Lunceford, Jared1; Joe, Andrew1; Cheng, Jonathan1; Webber, Andrea L.1; Ibrahim, Nageatte1; Plimack, Elizabeth R.2; Ott, Patrick A.3; Seiwert, Tanguy4; Ribas, Antoni5; McClanahan, Terrill K.1; Tomassini, Joanne E.1; Loboda, Andrey1; Kaufman, David1,6 | |
2018-10-12 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 362期号:6411页码:197-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a Tcell-inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab. TMB and GEP were independently predictive of response and demonstrated low correlation, suggesting that they capture distinct features of neoantigenicity and Tcell activation. Analysis of The Cancer Genome Atlas database showed TMB and GEP to have a low correlation, and analysis by joint stratification revealed biomarker-defined patterns of targetable-resistance biology. These biomarkers may have utility in clinical trial design by guiding rational selection of anti-PD-1 monotherapy and combination immunotherapy regimens. |
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:000447337200046 |
WOS关键词 | CELL LUNG-CANCER ; MISMATCH-REPAIR DEFICIENCY ; PROGRAMMED DEATH LIGAND-1 ; SEQUENCING DATA ; MUTATIONAL PROCESSES ; METASTATIC MELANOMA ; SOMATIC MUTATIONS ; CLINICAL-RESPONSE ; CTLA-4 BLOCKADE ; COPY NUMBER |
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/199826 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Merck & Co Inc, Kenilworth, NJ 07033 USA; 2.Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA; 3.Dana Farber Canc Inst, Boston, MA 02215 USA; 4.Univ Chicago, Chicago, IL 60637 USA; 5.Univ Calif Los Angeles, Los Angeles, CA 90095 USA; 6.Bill & Melinda Gates Med Res Inst, Cambridge, MA 02139 USA |
推荐引用方式 GB/T 7714 | Cristescu, Razvan,Mogg, Robin,Ayers, Mark,et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy[J]. SCIENCE,2018,362(6411):197-+. |
APA | Cristescu, Razvan.,Mogg, Robin.,Ayers, Mark.,Albright, Andrew.,Murphy, Erin.,...&Kaufman, David.(2018).Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy.SCIENCE,362(6411),197-+. |
MLA | Cristescu, Razvan,et al."Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy".SCIENCE 362.6411(2018):197-+. |
条目包含的文件 | 条目无相关文件。 |
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