HIF1α epigenetically repressed macrophages via CRISPR/Cas9-EZH2 system for enhanced cancer immunotherapy

作     者：Yan Dong Siyan Zhang Xiaotong Gao Dandan Yin Tingting Wang Zhelong Li Zhuo Wan Mengying Wei Ying Luo Guodong Yang Li Liu 

作者机构：Department of HematologyTangdu HospitalFourth Military Medical UniversityXi’an710038People’s Republic of China Department of Ultrasound DiagnosticsTangdu HospitalFourth Military Medical UniversityXi’an710038People’s Republic of China State Key Laboratory of Cancer BiologyFourth Military Medical UniversityXi’an710032People’s Republic of China Department of Biochemistry and Molecular BiologyFourth Military Medical UniversityXi’an710032People’s Republic of China Department of PathophysiologyFourth Military Medical UniversityXi’an710032People’s Republic of China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2021年第6卷第9期

页      面：2870-2880页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1002[医学-临床医学] 0805[工学-材料科学与工程（可授工学、理学学位）] 100214[医学-肿瘤学] 0836[工学-生物工程] 10[医学] 

基　　金：This work was funded by the National Natural Science Foundation of China(NSFC31573244 to L Liu,NSFC31771507 and NSFC81970737 to G Yang) Key Projects of Shaanxi Province(2018ZDXM-SF-063 to L Liu) 

主　　题：Cancer immunotherapy Immune suppressive microenvironment Macrophage HIF1α CRISPR/dCas9 Epigenetically reprogrammed macrophage 

摘      要：Immune suppressive microenvironment in tumor emerges as the main obstacle for cancer *** this study,we identified that HIF1α was activated in the tumor associated macrophages and acted as an important factor for the immune suppressive *** silencing of Hif1αvia histone H3 methylation in the promoter region was achieved by CRISPR/dCas9-EZH2 system,in which histone H3 methylase EZH2 was recruited to the promoter region *** Hif1αsilenced macrophage,namely HERM(Hif1αEpigenetically Repressed Macrophage)manifested as inheritable tumor suppressing *** the subcutaneous B16-F10 melanoma syngeneic model,intratumoral injection of HERMs reprogrammed the immune suppressive microenvironment to the active one,reducing tumor burden and prolonging overall ***,HERMs therapy remarkably inhibited tumor ***,our study has not only identified a promising cellular and molecular target for reverting immune suppressive microenvironment,but also provided a potent strategy for reprogramming tumor microenvironment via epigenetically reprogrammed macrophages.