| Accession |
PRJCA004965 |
| Title |
Tumor evolution selectively inactivates the core microRNA machinery for immune evasion |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
Raw sequence reads
|
| Organisms |
Mus musculus
|
| Description |
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. |
| Sample scope |
Multiisolate |
| Release date |
2021-09-15 |
| Biomaterial provider |
Cang Yong Lab |
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
Young Scientists Fund
|
82003803
|
|
| China Postdoctoral Science Foundation
|
|
2020T130669
|
|
| China Postdoctoral Science Foundation
|
|
2019M651613
|
|
|
|
| Submitter |
Tian-Yu
Song (songtianyu@zju.edu.cn)
|
| Organization |
ShanghaiTech University |
| Submission date |
2021-05-07 |
