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Targeting VCP potentiates immune checkpoint therapy for colorectal cancer

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收录情况： ◇ SCIE

作者：
Fang Wang[1] * ; Qi Qi[1,2] * ; Baifu Qin[3,4] * ; Yiwei Wang[5] ; Youwei Huang[1,6,7] ; Qing Li[1] ; Xi Shen[1] ; Xiangyu Wang[1] ; Shangqi Yang[1] ; Guopeng Pan[1] ; Jiahong Chen[1,8] ; Zixi Qin[1] ; Xueqin Chen[1] ; Yuqing Yang[1] ; Yuequan Zeng[1] ; Jun Liu[1] ; Yuqin Li[1] ; Ying Li[1] ; Zexiong Cheng[1] ; Xi Lin[1] ; Fan Xing[9] ; Yubo Zhang[1] ; Guocai Wang[10] ; Kai Li[4] ; Zhenyou Jiang[5,11] ; Haipeng Zhang[1,11] ;
机构： [1]Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China [2]MOE Key Laboratory of Tumor Molecular Biology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China [3]Institute of Molecular and Medical Virology, Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention andControl, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China [4]Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510655,China [5]Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China [6]Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai,Guangdong 519000, China [7]Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, Guangdong 510632,China [8]The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing 100191, China [9]Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China [10]Institute of Traditional Chinese Medicine & Natural Products, Guangdong Province Key Laboratory of Pharmacodynamic Constituents ofTCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China [11]Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
出处：
DOI： 10.1016/j.celrep.2023.113318
ISSN：

摘要：
Immune checkpoint blockade therapies are still ineffective for most patients with colorectal cancer (CRC). Immunogenic cell death (ICD) enables the release of key immunostimulatory signals to drive efficient anti-tumor immunity, which could be used to potentiate the effects of immune checkpoint inhibitors. Here, we showed that inhibition of valosin-containing protein (VCP) elicits ICD in CRC. Meanwhile, VCP inhibitor upregulates PD-L1 expression and compromises anti-tumor immunity in vivo. Mechanistically, VCP transcriptionally regulates PD-L1 expression in a JAK1-dependent manner. Combining VCP inhibitor with anti-PD1 remodels tumor immune microenvironment and reduces tumor growth in mouse models of CRC. Addition of oncolytic virus further augments the therapeutic activity of the combination regimen. Our study shows the molecular mechanism for regulating PD-L1 expression by VCP and suggests that inhibition of VCP has the potential to increase the efficacy of immunotherapy in CRC.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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出版当年[2022]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
JCR分区：
出版当年[2021]版：
Q1 CELL BIOLOGY
最新[2023]版：
Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China [5]Department of Microbiology and Immunology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, China [11]Key Laboratory of Viral Pathogenesis & Infection Prevention and Control (Jinan University), Ministry of Education, Guangzhou 510632, China
推荐引用方式(GB/T 7714)：
Fang Wang,Qi Qi,Baifu Qin,et al.Targeting VCP potentiates immune checkpoint therapy for colorectal cancer[J].CELL REPORTS.2023,42(11):113318.doi:10.1016/j.celrep.2023.113318.
APA：
Fang Wang,Qi Qi,Baifu Qin,Yiwei Wang,Youwei Huang...&Haipeng Zhang.(2023).Targeting VCP potentiates immune checkpoint therapy for colorectal cancer.CELL REPORTS,42,(11)
MLA：
Fang Wang,et al."Targeting VCP potentiates immune checkpoint therapy for colorectal cancer".CELL REPORTS 42..11(2023):113318

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