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

Sci Adv. 2022 Dec 9;8(49):eadd0005. doi: 10.1126/sciadv.add0005. Epub 2022 Dec 7.

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.

MeSH terms

  • Breast Neoplasms* / genetics
  • CD8-Positive T-Lymphocytes
  • Female
  • Gain of Function Mutation
  • Humans
  • Immunity
  • Melanoma* / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding