Genome-wide gain-of-function screening characterized lncRNAs as tumor immune response regulators [CRISPR_screen]

The majority of lncRNAs’ roles in tumor immunology remain elusive. In this project, we performed a CRISPR activation screening of 9744 lncRNAs in melanoma cells co-culturing with human CD8+ T cells. We identified 16 novel 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 upregulation 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. CRISPR activation sgRNA library targeting lncRNAs was transduced in MEL-526 cells and co-cultured with T cells before sequencing to determine sgRNA distribution