Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus.
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ABSTRACT:
SUBMITTER: Mineo M
PROVIDER: S-EPMC7377926 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We studied the molecules involved in downstream signaling induced by interferons to regulate PD- L1 and PD-L2 expression using a shRNA screen, Western blot, mRNAexpression profiling, promoter truncation analysis and chromatin immunoprecipitation.These studies revealed that the interferon gamma-JAK1/2-STAT1-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter. PD-L2 responded equally to interferon beta and gamma, and shared regulation through IRF1 and alsoSTAT3, which bind to the PD-L2 promoter. Analysis of biopsies from patients with melanoma confirmed interferon signature enrichment and upregulation of gene targets for STAT1/2/3 and IRF1 in anti-PD-1 responding tumors. Therefore, these studies map the signaling pathway of interferon-inducible PD-1 ligand expression
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