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Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE96619 | GEO | 2017/05/09

SECONDARY ACCESSION(S): PRJNA379183

REPOSITORIES: GEO

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