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
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  (
Organization ShanghaiTech University
Submission date 2021-05-07

Project Data

Resource name Description
BioSample (103)  show -
GSA (4) -
CRA004141 RNASeq for Clonal Mutation Profiling
CRA004140 RNASeq of Ankrd52 KO MC38 tumor cells
CRA004145 T cell co-culture CRISPR screen targeting profiled tumor heterogeneity
CRA004146 In vivo CRISPR screen targeting profiled tumor heterogeneity