中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
DKK2 imparts tumor immunity evasion through beta-catenin-independent suppression of cytotoxic immune-cell activation

文献类型:期刊论文

作者Xiao, Qian1,2; Wang, Wei-Jia1,2; Zheng, Yingxia1,2; Sahraei, Mahnaz1,2; Tang, Wenwen1,2; Wu, Dianqing1,2,8; Wu, Jibo3; Li, Lin3; Chen, Shiyang4; Yu, Xiaoqing5
刊名NATURE MEDICINE
出版日期2018
卷号24期号:3页码:262-+
关键词Intestinal Intraepithelial Lymphocytes Wnt Signaling Pathway Wnt/beta-catenin Cancer-immunotherapy Colorectal-cancer Nk Cells Therapy Differentiation Interleukin-15 Resistance
ISSN号1078-8956
DOI10.1038/nm.4496
文献子类Article
英文摘要

Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion. DKK2 secreted by tumor cells acts on cytotoxic lymphocytes, inhibiting STAT5 signaling by impeding STAT5 nuclear localization via LRP5, but independently of LRP6 and the Wnt-beta-catenin pathway. Genetic or antibody-mediated ablation of DKK2 activates natural killer (NK) cells and CD8(+) T cells in tumors, impedes tumor progression, and enhances the effects of PD-1 blockade. Thus, we have identified a previously unknown tumor immune-suppressive mechanism and immunotherapeutic targets particularly relevant for CRCs and a subset of melanomas.

电子版国际标准刊号1546-170X
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology ; Medicine, Research & Experimental
语种英语
WOS记录号WOS:000426700900008
版本出版稿
源URL[http://202.127.25.143/handle/331003/3392]  
专题生化所2018年发文
通讯作者Tang, Wenwen; Wu, Dianqing; Li, Lin
作者单位1.Yale Sch Med, Vasc Biol & Therapeut Program, New Haven, CT USA;
2.Yale Sch Med, Dept Pharmacol, New Haven, CT USA;
3.Univ Chinese Acad Sci, State Key Lab Mol Biol,Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci,Shanghai Inst Bio, Innovat Ctr Cell Signaling Network,Inst Biochem &, Shanghai, Peoples R China;
4.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai, Peoples R China;
5.Yale Univ, Biostat Dept, New Haven, CT USA;
6.Yale Sch Med, Dept Dermatol, New Haven, CT USA;
7.Yale Sch Med, Dept Pathol, New Haven, CT USA;
8.Yale Sch Med, Dept Immunol, New Haven, CT USA;
9.Yale Sch Med, Yale Canc Ctr, New Haven, CT USA;
10.Univ Vet Med Vienna, Dept Biomed Sci, Inst Pharmacol & Toxicol, Vienna, Austria;
推荐引用方式
GB/T 7714
Xiao, Qian,Wang, Wei-Jia,Zheng, Yingxia,et al. DKK2 imparts tumor immunity evasion through beta-catenin-independent suppression of cytotoxic immune-cell activation[J]. NATURE MEDICINE,2018,24(3):262-+.
APA Xiao, Qian.,Wang, Wei-Jia.,Zheng, Yingxia.,Sahraei, Mahnaz.,Tang, Wenwen.,...&Sun, Le.(2018).DKK2 imparts tumor immunity evasion through beta-catenin-independent suppression of cytotoxic immune-cell activation.NATURE MEDICINE,24(3),262-+.
MLA Xiao, Qian,et al."DKK2 imparts tumor immunity evasion through beta-catenin-independent suppression of cytotoxic immune-cell activation".NATURE MEDICINE 24.3(2018):262-+.

入库方式: OAI收割

来源:上海生物化学与细胞生物学研究所

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