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DOI | 10.1126/science.aao1710 |
A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing | |
Pan, Deng1; Kobayashi, Aya1,2; Jiang, Peng3; de Andrade, Lucas Ferrari1; Tay, Rong En1; Luoma, Adrienne M.1; Tsoucas, Daphne3; Qiu, Xintao4; Lim, Klothilda4; Rao, Prakash4; Long, Henry W.4; Yuan, Guo-Cheng3; Doench, John5; Brown, Myles4; Liu, X. Shirley3; Wucherpfennig, Kai W.1,6 | |
2018-02-16 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 359期号:6377页码:770-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Japan |
英文摘要 | Many human cancers are resistant to immunotherapy, for reasons that are poorly understood. We used a genome-scale CRISPR-Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of antitumor immunity. Inactivation of >100 genes-including Pbrm1, Arid2, and Brd7, which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex-sensitized mouse B16F10 melanoma cells to killing by T cells. Loss of PBAF function increased tumor cell sensitivity to interferon-g, resulting in enhanced secretion of chemokines that recruit effector T cells. Treatment-resistant tumors became responsive to immunotherapy when Pbrm1 was inactivated. In many human cancers, expression of PBRM1 and ARID2 inversely correlated with expression of T cell cytotoxicity genes, and Pbrm1-deficient murine melanomas were more strongly infiltrated by cytotoxic T cells. |
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:000425116200039 |
WOS关键词 | CANCER-IMMUNOTHERAPY ; ACQUIRED-RESISTANCE ; ANTITUMOR-ACTIVITY ; IMMUNE-SYSTEM ; B7 FAMILY ; MELANOMA ; COMBINATION ; MUTATIONS ; BLOCKADE ; GENES |
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/197993 |
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, Boston, MA 02215 USA; 2.Astellas Pharma, Tokyo 1038411, Japan; 3.Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA; 4.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA; 5.Broad Inst MIT & Harvard, Genet Perturbat Platform, Cambridge, MA 02142 USA; 6.Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA |
推荐引用方式 GB/T 7714 | Pan, Deng,Kobayashi, Aya,Jiang, Peng,et al. A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing[J]. SCIENCE,2018,359(6377):770-+. |
APA | Pan, Deng.,Kobayashi, Aya.,Jiang, Peng.,de Andrade, Lucas Ferrari.,Tay, Rong En.,...&Wucherpfennig, Kai W..(2018).A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing.SCIENCE,359(6377),770-+. |
MLA | Pan, Deng,et al."A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing".SCIENCE 359.6377(2018):770-+. |
条目包含的文件 | 条目无相关文件。 |
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