The loss of RNA N-6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8(+) T cell dysfunction and tumor growth
文献类型：期刊论文
| 作者 | Dong, Lihui; Chen, Chuanyuan; Zhang, Yawei; Guo, Peijin; Wang, Zhenghang; Li, Jian; Liu, Yi; Liu, Jun; Chang, Renbao; Li, Yilin |
| 刊名 | CANCER CELL
 |
| 出版日期 | 2021-07-12 |
| 卷号 | 39期号:7页码:945-+ |
| ISSN号 | 1535-6108 |
| 英文摘要 | Tumor-associated macrophages (TAMs) can dampen the antitumor activity of T cells, yet the underlying mechanism remains incompletely understood. Here, we show that C1q(+) TAMs are regulated by an RNA N-6-methyladenosine (m(6)A) program and modulate tumor-infiltrating CD8(+) T cells by expressing multiple immunomodulatory ligands. Macrophage-specific knockout of an m(6)A methyltransferase Mettl14 drives CD8(+) T cell differentiation along a dysfunctional trajectory, impairing CD8(+) T cells to eliminate tumors. Mettl14-deficient C1q(+) TAMs show a decreased m(6)A abundance on and a higher level of transcripts of Ebi3, a cytokine subunit. In addition, neutralization of EBI3 leads to reinvigoration of dysfunctional CD8(+) T cells and overcomes immunosuppressive impact in mice. We show that the METTL14-m(6)A levels are negatively correlated with dysfunctional T cell levels in patients with colorectal cancer, supporting the clinical relevance of this regulatory pathway. Thus, our study demonstrates how an m(6)A methyltransferase in TAMs promotes CD8(+) T cell dysfunction and tumor progression. |
| WOS研究方向 | Oncology ; Cell Biology |
| 源URL | [http://ir.rcees.ac.cn/handle/311016/45627]  |
| 专题 | 生态环境研究中心_大气污染控制中心 |
| 作者单位 | 1.Tsinghua Univ, THU PKU Ctr Life Sci, Sch Med, Inst Immunol,Dept Basic Med Sci,Beijing Key Lab I, Beijing 100084, Peoples R China 2.Chinese Acad Sci, Key Lab Genom & Precis Med, Beijing Inst Genom, Beijing 100101, Peoples R China 3.Chinese Acad Sci, China Natl Ctr Bioinformat, Beijing 100101, Peoples R China 4.Univ Chinese Acad Sci, Coll Future Technol, Sino Danish Coll, Beijing 100049, Peoples R China 5.Peking Univ Canc Hosp & Inst, Minist Educ, Key Lab Carcinogenesis & Translat Res, Dept Gastrointestinal Oncol, Beijing 100142, Peoples R China 6.Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dong, Lihui,Chen, Chuanyuan,Zhang, Yawei,et al. The loss of RNA N-6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8(+) T cell dysfunction and tumor growth[J]. CANCER CELL,2021,39(7):945-+. |
| APA | Dong, Lihui.,Chen, Chuanyuan.,Zhang, Yawei.,Guo, Peijin.,Wang, Zhenghang.,...&Han, Dali.(2021).The loss of RNA N-6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8(+) T cell dysfunction and tumor growth.CANCER CELL,39(7),945-+. |
| MLA | Dong, Lihui,et al."The loss of RNA N-6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8(+) T cell dysfunction and tumor growth".CANCER CELL 39.7(2021):945-+. |
入库方式： OAI收割
来源：生态环境研究中心
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