中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
PRMT1 Inhibition Activates the Interferon Pathway to Potentiate Antitumor Immunity and Enhance Checkpoint Blockade Efficacy in Melanoma

文献类型：期刊论文

作者Tao, Hongru10; Jin, Chen9; Zhou, Liyuan6,7,8; Deng, Zhenzhong5; Li, Xiao6,8; Dang, Wenzhen6,8; Fan, Shijie4; Li, Bing6,7; Ye, Fei3; Lu, Junyan2
刊名CANCER RESEARCH
出版日期2024-02-01
卷号84期号:3页码:419-433
ISSN号0008-5472
DOI10.1158/0008-5472.CAN-23-1082
通讯作者Liu, Chuanpeng(zhangyy@simm.ac.cn) ; Luo, Cheng(cluo@simm.ac.cn) ; Zhang, Yuanyuan(liucp74@hotmail.com)
英文摘要Despite the immense success of immune checkpoint blockade (ICB) in cancer treatment, many tumors, including melanoma, exhibit innate or adaptive resistance. Tumor-intrinsic T-cell deficiency and T-cell dysfunction have been identified as essential factors in the emergence of ICB resistance. Here, we found that protein arginine methyltransferase 1 (PRMT1) expression was inversely correlated with the number and activity of CD8(+) T cells within melanoma specimen. PRMT1 deficiency or inhibition with DCPT1061 significantly restrained refractory melanoma growth and increased intratumoral CD8(+) T cells in vivo. Moreover, PRMT1 deletion in melanoma cells facilitated formation of double-stranded RNA derived from endogenous retroviral elements (ERV) and stimulated an intracellular interferon response. Mechanistically, PRMT1 deficiency repressed the expression of DNA methyltransferase 1 (DNMT1) by attenuating modification of H4R3me2a and H3K27ac at enhancer regions of Dnmt1, and DNMT1 downregulation consequently activated ERV transcription and the interferon signaling. Importantly, PRMT1 inhibition with DCPT1061 synergized with PD-1 blockade to suppress tumor progression and increase the proportion of CD8(+) T cells as well as IFN gamma(+)CD8(+) T cells in vivo. Together, these results reveal an unrecognized role and mechanism of PRMT1 in regulating antitumor T-cell immunity, suggesting PRMT1 inhibition as a potent strategy to increase the efficacy of ICB. Significance: Targeting PRMT1 stimulates interferon signaling by increasing expression of endogenous retroviral elements and double-stranded RNA through repression of DNMT1, which induces antitumor immunity and synergizes with immunotherapy to suppress tumor progression. [GRAPHICS] .
WOS关键词CD8 T-CELLS ; ARGININE METHYLTRANSFERASES ; METHYLATION ; PD-1 ; CANCER ; IMMUNOTHERAPY ; EXPRESSION ; TARGET ; CARM1
资助项目National Natural Science Foundation of China (NSFC)[82273946] ; National Natural Science Foundation of China (NSFC)[U23A20108] ; National Natural Science Foundation of China (NSFC)[21820102008] ; National Natural Science Foundation of China (NSFC)[81821005] ; National Natural Science Foundation of China (NSFC)[92253303] ; National Natural Science Foundation of China[23ZR1475100] ; Science and Technology Commission of Shanghai Municipality[2022YFC3400500] ; Science and Technology Commission of Shanghai Municipality[2021ZD0203900] ; National Key R&D Program of China[SKLRD-OP-202213] ; National Key R&D Program of China[LG-QS-202206-07] ; Open Project of State Key Laboratory of Respiratory Disease ; National Multidisciplinary Innovation Team of Traditional Chinese Medicine[ZYYCXTD-202004] ; National Administration of Traditional Chinese Medicine[2019B090904008] ; High-level new RD institute[2021B0909050003] ; High-level Innovative Research Institute
WOS研究方向Oncology
语种英语
出版者AMER ASSOC CANCER RESEARCH
WOS记录号WOS:001155666500008
源URL[http://119.78.100.183/handle/2S10ELR8/309886]  
专题中国科学院上海药物研究所
通讯作者Liu, Chuanpeng; Luo, Cheng; Zhang, Yuanyuan
作者单位1.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, Guangzhou, Peoples R China
2.Heidelberg Univ, Med Fac Heidelberg, Heidelberg, Germany
3.Zhejiang Sci Tech Univ, Coll Life Sci & Med, Hangzhou, Peoples R China
4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China
5.Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Oncol, Shanghai, Peoples R China
6.Univ Chinese Acad Sci, Beijing, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Ctr Chem Biol,State Key Lab Drug Res, Shanghai, Peoples R China
8.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China
9.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China
10.Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150001, Peoples R China
推荐引用方式
GB/T 7714		 Tao, Hongru,Jin, Chen,Zhou, Liyuan,et al. PRMT1 Inhibition Activates the Interferon Pathway to Potentiate Antitumor Immunity and Enhance Checkpoint Blockade Efficacy in Melanoma[J]. CANCER RESEARCH,2024,84(3):419-433.
APA Tao, Hongru.,Jin, Chen.,Zhou, Liyuan.,Deng, Zhenzhong.,Li, Xiao.,...&Zhang, Yuanyuan.(2024).PRMT1 Inhibition Activates the Interferon Pathway to Potentiate Antitumor Immunity and Enhance Checkpoint Blockade Efficacy in Melanoma.CANCER RESEARCH,84(3),419-433.
MLA Tao, Hongru,et al."PRMT1 Inhibition Activates the Interferon Pathway to Potentiate Antitumor Immunity and Enhance Checkpoint Blockade Efficacy in Melanoma".CANCER RESEARCH 84.3(2024):419-433.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。