Genome-wide gain-of-function screening characterized lncRNAs as tumor immune response regulators [CRISPR_screen]. 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. Overall design: CRISPR activation sgRNA library targeting lncRNAs was transduced in MEL-526 cells and co-cultured with T cells before sequencing to determine sgRNA distribution