| 项目编号 |
PRJCA004965 |
| 项目标题 |
Tumor evolution selectively inactivates the core microRNA machinery for immune evasion |
| 涉及领域 |
Medical |
| 数据类型 |
Transcriptome or Gene expression
Raw sequence reads
|
| 物种名称 |
Mus musculus
|
| 描述信息 |
Cancer cells acquire genetic heterogeneity to escape from immune surveillance during tumor evolution, but a systematic approach to distinguish emerging driver from passenger mutations is lacking. Here we investigate the impact of different immune pressure on tumor clonal dynamics and immune evasion mechanism by combining massive parallel sequencing of immune edited murine tumors and targeted CRISPR library screens in xenograft and co-culture systems. We find that the activity of the core microRNA (miRNA) biogenesis and targeting machinery maintains the sensitivity of cancer cells to PD-1-independent T cell-mediated cytotoxicity. Inactivation of the machinery or introduction of its frequent mutations found in patients dampens the JAK-STAT-interferon-γ signaling, chemokine expression and antigen presentation in cancer cells, largely by abolishing miRNA-targeted silencing of suppressor of cytokine signaling 1 (SOCS1). In nearly all human cancer types, expression of each miRNA machinery component strongly correlates with intratumoral T cell infiltration. Our data indicate that the evolutionarily conserved miRNA pathway is exploited by cancer cells for escape from immune elimination and T cell-based immunotherapy. |
| 样品范围 |
Multiisolate |
| 发布日期 |
2021-09-15 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 34853298
|
Tumor evolution selectively inactivates the core microRNA machinery for immune evasion
|
Nature Communications
|
10.1038/s41467-021-27331-3
|
2021
|
|
|
| 实验材料提供者 |
Cang Yong Lab |
| 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)
|
Young Scientists Fund
|
82003803
|
|
| China Postdoctoral Science Foundation
|
|
2020T130669
|
|
| China Postdoctoral Science Foundation
|
|
2019M651613
|
|
|
|
| 提交者 |
Tian-Yu
Song (songtianyu@zju.edu.cn)
|
| 提交单位 |
ShanghaiTech University |
| 提交日期 |
2021-05-07 |
