Genome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response

全基因组功能获得性筛选鉴定了肿瘤免疫反应的lncRNA调控因子

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作者:Yifei Wang ,Yueshan Zhao ,Weiwei Guo ,Ghanshyam Singh Yadav ,Chetana Bhaskarla ,Zehua Wang ,Xiaofei Wang ,Sihan Li ,Yue Wang ,Yuang Chen ,Dhamotharan Pattarayan ,Wen Xie ,Song Li ,Binfeng Lu ,Udai S Kammula ,Min Zhang ,Da Yang

Abstract

The majority of lncRNAs' roles in tumor immunology remain elusive. This project performed a CRISPR activation screening of 9744 lncRNAs in melanoma cells cocultured with human CD8+ T cells. We identified 16 lncRNAs potentially regulating tumor immune response. Further integrative analysis using tumor immunogenomics data revealed that IL10RB-DT and LINC01198 are significantly correlated with tumor immune response and survival in melanoma and breast cancer. Specifically, IL10RB-DT suppresses CD8+ T cells activation via inhibiting IFN-γ-JAK-STAT1 signaling and antigen presentation in melanoma and breast cancer cells. On the other hand, LINC01198's up-regulation sensitizes the killing of tumor cells by CD8+ T cells. Mechanistically, LINC01198 interacts and activates NF-κB component p65 to trigger the type I and type II interferon responses in melanoma and breast cancer cells. Our study systematically characterized novel lncRNAs involved in tumor immune response.

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