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DOI | 10.1126/science.aau0447 |
CANCER Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response | |
Mandal, Rajarsi1,2,3,13; Samstein, Robert M.3,4; Lee, Ken-Wing3; Havel, Jonathan J.3,5; Wang, Hao6; Krishna, Chirag7; Sabio, Erich Y.3; Makarov, Vladimir3,5; Kuo, Fengshen5; Blecua, Pedro4; Ramaswamy, Apoorva T.8; Durham, Jennifer N.2,6,9; Bartlett, Bjarne9; Ma, Xiaoxiao3; Srivastava, Raghvendra5; Middha, Sumit10; Zehir, Ahmet10; Hechtman, Jaclyn F.10; Morris, Luc G. T.3,5,11; Weinhold, Nils4; Riaz, Nadeem3,4,5; Le, Dung T.2,6,9; Diaz, Luis A., Jr.5,12; Chan, Timothy A.3,4,5 | |
2019-05-03 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6439页码:485-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Tumors with mismatch repair deficiency (MMR-d) are characterized by sequence alterations in microsatellites and can accumulate thousands of mutations. This high mutational burden renders tumors immunogenic and sensitive to programmed cell death-1 (PD-1) immune checkpoint inhibitors. Yet, despite their tumor immunogenicity, patients with MMR-deficient tumors experience highly variable responses, and roughly half are refractory to treatment. We present experimental and clinical evidence showing that the degree of microsatellite instability (MSI) and resultant mutational load, in part, underlies the variable response to PD-1 blockade immunotherapy in MMR-d human and mouse tumors. The extent of response is particularly associated with the accumulation of insertion-deletion (indel) mutational load. This study provides a rationale for the genome-wide characterization of MSI intensity and mutational load to better profile responses to anti-PD-1 immunotherapy across MMR-deficient human cancers. |
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:000466809600034 |
WOS关键词 | MICROSATELLITE INSTABILITY DETECTION ; MUTATIONAL LANDSCAPE ; CTLA-4 BLOCKADE ; PD-1 BLOCKADE ; GENERATION |
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/201354 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA; 2.Johns Hopkins, Bloomberg Kimmel Inst Canc Immunotherapy, Baltimore, MD 21287 USA; 3.Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA; 4.Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA; 5.Mem Sloan Kettering Canc Ctr, Immunogen & Precis Oncol Platform, New York, NY 10065 USA; 6.Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA; 7.Mem Sloan Kettering Canc Ctr, Computat & Syst Biol Program, New York, NY 10065 USA; 8.Weill Cornell New York Presbyterian Hosp, Dept Otolaryngol Head & Neck Surg, New York, NY 10065 USA; 9.Johns Hopkins, Swim Across Amer Lab, Baltimore, MD 21287 USA; 10.Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA; 11.Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY 10065 USA; 12.Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, New York, NY 10065 USA; 13.Johns Hopkins, Bloomberg Kimmel Inst Canc Immunotherapy, Johns Hopkins Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA |
推荐引用方式 GB/T 7714 | Mandal, Rajarsi,Samstein, Robert M.,Lee, Ken-Wing,et al. CANCER Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response[J]. SCIENCE,2019,364(6439):485-+. |
APA | Mandal, Rajarsi.,Samstein, Robert M..,Lee, Ken-Wing.,Havel, Jonathan J..,Wang, Hao.,...&Chan, Timothy A..(2019).CANCER Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response.SCIENCE,364(6439),485-+. |
MLA | Mandal, Rajarsi,et al."CANCER Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response".SCIENCE 364.6439(2019):485-+. |
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