Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response
文献类型：期刊论文
| 作者 | Tan, Lianmei7; Yin, Tao6,7; Xiang, Handan7; Wang, Liuyang5; Mudgal, Poorva4; Chen, Junying7; Ding, Yi7; Wang, Guoping6; Lim, Bryan Jian Wei6; Huang, Yuqi3 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2024-10-03 |
| 卷号 | 15期号:1页码:15 |
| DOI | 10.1038/s41467-024-52902-5 |
| 通讯作者 | Li, Qi-Jing(Li_QiJing@imcb.a-star.edu.sg) ; Wang, Xiao-Fan(xiao.fan.wang@duke.edu) |
| 英文摘要 | Immunotherapy successfully complements traditional cancer treatment. However, primary and acquired resistance might limit efficacy. Reduced antigen presentation by MHC-I has been identified as potential resistance factor. Here we show that the epigenetic regulator ubiquitin-like with PHD and ring finger domains 1 (UHRF1), exhibits altered expression and aberrant cytosolic localization in cancerous tissues, where it promotes MHC-I ubiquitination and degradation. Cytoplasmic translocation of UHRF1 is induced by its phosphorylation on a specific serine in response to signals provided by factors present in the tumor microenvironment (TME), such as TGF-beta, enabling UHRF1 to bind MHC-I. Downregulation of MHC-I results in suppression of the antigen presentation pathway to establish an immune hostile TME. UHRF1 inactivation by genetic deletion synergizes with immune checkpoint blockade (ICB) treatment and induces an anti-tumour memory response by evoking low-affinity T cells. Our study adds to the understanding of UHRF1 in cancer immune evasion and provides a potential target to synergize with immunotherapy and overcome immunotherapeutic resistance. MHC-I mediated antigen presentation is an important element of the anti-tumour immune response. Here authors identify a tumour immune escape mechanism by which the cancer cells express the ubiquitin E3 ligase UHRF1 in the cytoplasm instead of the nuclear expression pattern observed in normal tissues, and this results in degradation of MHC-I and thus diminished antigen presentation and anti-tumour T cell response. |
| WOS关键词 | ACQUIRED-RESISTANCE ; CELL CARCINOMA ; TGF-BETA ; TUMOR ; AFFINITY ; BLOCKADE ; EXCLUSION ; MARKER ; GAMMA ; CD69 |
| 资助项目 | U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)[BioRender.com/j18n557] ; U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)[R01-CA233205] ; NIH ; BMRC[NRFI09-0016] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001328657100011 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/314044]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Qi-Jing; Wang, Xiao-Fan |
| 作者单位 | 1.ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore 2.ASTAR, Inst Mol & Cell Biol IMCB, Singapore, Singapore 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 4.TCRCure Biopharm, Durham, NC USA 5.Duke Univ, Sch Med, Dept Mol Genet & Microbiol, Durham, NC USA 6.Duke Univ, Sch Med, Dept Immunol, Durham, NC 27708 USA 7.Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27708 USA |
| 推荐引用方式 GB/T 7714 | Tan, Lianmei,Yin, Tao,Xiang, Handan,et al. Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response[J]. NATURE COMMUNICATIONS,2024,15(1):15. |
| APA | Tan, Lianmei.,Yin, Tao.,Xiang, Handan.,Wang, Liuyang.,Mudgal, Poorva.,...&Wang, Xiao-Fan.(2024).Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response.NATURE COMMUNICATIONS,15(1),15. |
| MLA | Tan, Lianmei,et al."Aberrant cytoplasmic expression of UHRF1 restrains the MHC-I-mediated anti-tumor immune response".NATURE COMMUNICATIONS 15.1(2024):15. |
入库方式： OAI收割
来源：上海药物研究所
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