GSTDTAP  > 地球科学
DOI10.1126/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
ISSN0036-8075
EISSN1095-9203
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
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引用统计
被引频次:632[WOS]   [WOS记录]     [WOS相关记录]
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
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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-+.
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