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

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 <i>IL10RB-DT</i> and <i>LINC01198</i> are significantly correlated with tumor immune response and survival in melanoma and breast cancer. Specifically, <i>IL10RB-DT</i> 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, <i>LINC01198</i>'s up-regulation sensitizes the killing of tumor cells by CD8⁺ T cells. Mechanistically, <i>LINC01198</i> 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.