biostudies-literatureWang YNCI NIH HHSeadd0005https://www.ebi.ac.uk/biostudies/studies/S-EPMC9728976biostudies-literatureUnknown8(49)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, Science advancesGenome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response.PMC9728976R01 CA255196R01 CA222274R01 CA233521Pattarayan DXie WGuo WBhaskarla CZhang MYang DYadav GSZhao YLu BLi SKammula USChen YWang XWang YWang ZfalseGenome-wide gain-of-function screening characterized lncRNA regulators for tumor immune response.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, 2022-01-01T00:00:00Z2022 Dec2026-06-04T12:27:35.771Z2025-02-18T23:25:53.899ZS-EPMC97289763647579710.1126/sciadv.add0005