Genome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response
Yifei Wang, Yueshan Zhao, Weiwei Guo, Ghanshyam S. 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.