机构：[1]Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang,China[2]Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX[3]Department of Biological Sciences,Dong-A University, Busan, Republic of Korea[4]The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, China[5]Department ofNeurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, Zhejiang, China[6]Key Laboratory of Diagnosis andTreatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou,Zhejiang, China[7]Department of Respiratory Medicine, Sir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine,Hangzhou, Zhejiang, China[8]Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease of The First AffiliatedHospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China浙江大学医学院附属第一医院[9]State Key Laboratory of Oral Diseases, National ClinicalResearch Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China[10]Department of Nutrition and Food Hygiene, Centerfor Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China[11]Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, China[12]ChineseAcademy of Sciences Key Laboratory of Infection and Immunity, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics, ChineseAcademy of Sciences, Beijing, China[13]College of Dentistry, Dankook University, Cheonan, Republic of Korea[14]School of Life Sciences, Tsinghua University, Beijing,China[15]People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
PD-L1 up-regulation in cancer contributes to immune evasion by tumor cells. Here, we show that Wnt ligand and activated EGFR induce the binding of the β-catenin/TCF/LEF complex to the CD274 gene promoter region to induce PD-L1 expression, in which AKT activation plays an important role. β-Catenin depletion, AKT inhibition, or PTEN expression reduces PD-L1 expression in tumor cells, enhances activation and tumor infiltration of CD8+ T cells, and reduces tumor growth, accompanied by prolonged mouse survival. Combined treatment with a clinically available AKT inhibitor and an anti-PD-1 antibody overcomes tumor immune evasion and greatly inhibits tumor growth. In addition, AKT-mediated β-catenin S552 phosphorylation and nuclear β-catenin are positively correlated with PD-L1 expression and inversely correlated with the tumor infiltration of CD8+ T cells in human glioblastoma specimens, highlighting the clinical significance of β-catenin activation in tumor immune evasion.
This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.
基金：
This work was supported by the Zhejiang University Research Fund (188020*194221901/029; to Z. Lu); the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang (2019R01001; to Z. Lu); the National Research Foundation of Korea grant funded by the Korean government (MIST;2020R1C1C1011350); the Bio&Medical Technology Development Programfunded by theMinistry of Science, ICT and Future Planning, Republic of Korea (NRF-2017M3A9E4047243); National Natural Science Foundation of China (81902151; to L. Du);and Zhejiang Natural Science Foundation grant LQ19H160010 (to L. Du). Z. Lu is a Kuancheng Wang Distinguished Chair.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区医学
小类|1 区免疫学1 区医学：研究与实验
最新[2023]版：
大类|1 区医学
小类|1 区免疫学1 区医学：研究与实验
第一作者：
第一作者机构：[1]Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang,China[2]Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang,China[15]People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
推荐引用方式(GB/T 7714)：
Linyong Du,Jong-Ho Lee,Hongfei Jiang,et al.β-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion.[J].JOURNAL OF EXPERIMENTAL MEDICINE.2020,217(11):doi:10.1084/jem.20191115.
APA：
Linyong Du,Jong-Ho Lee,Hongfei Jiang,Chengde Wang,Silu Wang...&Jianxin Lyu.(2020).β-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion..JOURNAL OF EXPERIMENTAL MEDICINE,217,(11)
MLA：
Linyong Du,et al."β-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion.".JOURNAL OF EXPERIMENTAL MEDICINE 217..11(2020)
医学