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Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement

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作者：
Liu Jiaye[1,2,3,4] ; Wang Yang[5] ; Mu Chunyang[6] ; Li Meng[7,8] ; Li Kewei[9] ; Li Shan[10] ; Wu Wenshuang[1,2] ; Du Lingyao[11] ; Zhang Xiaoyun[6] ; Li Chuan[6] ; Peng Wei[6] ; Shen Junyi[6] ; Liu Yang[1,2] ; Yang Dujiang[12] ; Zhang Kaixiang[1,2] ; Ning Qingyang[1,2] ; Fu Xiaoying[12] ; Zeng Yu[13] ; Ni Yinyun[4] ; Zhou Zongguang[12] ; Liu Yi[14] ; Hu Yiguo[3] ; Zheng Xiaofeng[15] ; Wen Tianfu[16] ; Li Zhihui[17,18] ; Liu Yong[19] ;
机构： [1]Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, China. [2]Laboratory of Thyroid and Parathyroid diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. [3]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China. [4]Respiratory Health Institute, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. [5]Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. [6]Department of Liver Surgery &Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China. [7]Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. [8]Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Bioland Laboratory, Guangzhou, China. [9]Department of Pediatric Department, West China Hospital, Sichuan University, Chengdu, China. [10]Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China. [11]Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China. [12]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China. [13]Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. [14]Department of Rheumatology and Immunology, Rare Disease Center, West China Hospital, Sichuan University, Chengdu, China. [15]Department of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China [16]Department of Liver Surgery &Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, China. [17]Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, China. [18]Laboratory of Thyroid and Parathyroid diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. [19]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.
出处：
DOI： 10.1038/s41467-022-31928-7

摘要：
Cancer associated fibroblasts (CAFs) support tumors via multiple mechanisms, including maintaining the immunosuppressive tumor microenvironment and limiting infiltration of immune cells. The prolyl isomerase Pin1, whose overexpression in CAFs has not been fully profiled yet, plays critical roles in tumor initiation and progression. To decipher effects of selective Pin1 inhibition in CAFs on pancreatic cancer, here we formulate a DNA-barcoded micellular system (DMS) encapsulating the Pin1 inhibitor AG17724. DMS functionalized with CAF-targeting anti-FAP-α antibodies (antiCAFs-DMS) can selectively inhibit Pin1 in CAFs, leading to efficacious but transient tumor growth inhibition. We further integrate DNA aptamers (AptT), which can engage CD8+ T lymphocytes, to obtain a bispecific antiCAFs-DMS-AptT system. AntiCAFs-DMS-AptT inhibits tumor growth in subcutaneous and orthotopic pancreatic cancer models.© 2022. The Author(s).

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外文
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出版当年[2022]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2023]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
第一作者：
第一作者机构： [1]Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, China. [2]Laboratory of Thyroid and Parathyroid diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China. [3]State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China. [4]Respiratory Health Institute, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
共同第一作者：
通讯作者：
通讯机构： [17]Department of Thyroid and Parathyroid Surgery, West China Hospital, Sichuan University, Chengdu, China. [18]Laboratory of Thyroid and Parathyroid diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
推荐引用方式(GB/T 7714)：
Liu Jiaye,Wang Yang,Mu Chunyang,et al.Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement[J].Nature communications.2022,13(1):4308.doi:10.1038/s41467-022-31928-7.
APA：
Liu Jiaye,Wang Yang,Mu Chunyang,Li Meng,Li Kewei...&Liu Yong.(2022).Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement.Nature communications,13,(1)
MLA：
Liu Jiaye,et al."Pancreatic tumor eradication via selective Pin1 inhibition in cancer-associated fibroblasts and T lymphocytes engagement".Nature communications 13..1(2022):4308

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