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![]() |
刊名 | NATURE MEDICINE
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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 |
DOI | 10.1038/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-+. |
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