| 项目编号 |
PRJCA024070 |
| 项目标题 |
Tumor intrinsic METTL5 expression drives immune evasion to promote intrahepatic cholangiocarcinoma progression |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
|
| 物种名称 |
Homo sapiens
|
| 描述信息 |
Intrahepatic cholangiocarcinoma (ICC) is an aggressive and heterogeneous malignancy derived from biliary tract in liver, with poor prognosis and limited treatment options. Here, we unravel that METTL5, the 18S rRNA m6A methytransferase, promotes ICC progression via reshaping ICC tumor immune microenvironment. Biologically, liver-specific Mettl5 knockout (cKO) mice exhibited decreased ICC tumor burden compared to control mice, accompanied with increased anti-tumor IFN-γ+CD8+T cells and decreased infiltration of tumor-associated macrophages (TAMs) via single cell RNA sequencing (scRNAseq) analysis. Mechanistically, METTL5-mediated 18S rRNA m6A modification regulated the mRNA translation of chemokines that recruited CD8+T cells and TAMs, respectively. In human ICC, we validated that low METTL5 expression correlated with increased tumor anti-tumoral CD8+T cells and decreased pro-tumoral TAMs. Ultimately, targeting METTL5 using lipid nanoparticle encapsulated siRNA combined with anti-PD-1 therapy significantly provoked anti-tumor immunity and mitigated ICC progression in ICC mouse model, suggesting METTL5 as a promising therapeutic target for treating ICC. |
| 样品范围 |
Monoisolate |
| 发布日期 |
2025-10-21 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 41431992
|
METTL5 Enables Immune Evasion of Liver Cancer via Chemokine mRNA Translation Regulation
|
Advanced Science
|
10.1002/advs.202512528
|
2025
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Natural Science Foundation of China (NSFC)
|
Key Program
|
82130083
|
|
|
|
| 提交者 |
Ming
Kuang (kuangm@mail.sysu.edu.cn)
|
| 提交单位 |
The First Affiliated Hospital, Sun Yat-sen University |
| 提交日期 |
2024-03-05 |
