Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression.

نویسندگان

  • Angel Garcia-Diaz
  • Daniel Sanghoon Shin
  • Blanca Homet Moreno
  • Justin Saco
  • Helena Escuin-Ordinas
  • Gabriel Abril Rodriguez
  • Jesse M Zaretsky
  • Lu Sun
  • Willy Hugo
  • Xiaoyan Wang
  • Giulia Parisi
  • Cristina Puig Saus
  • Davis Y Torrejon
  • Thomas G Graeber
  • Begonya Comin-Anduix
  • Siwen Hu-Lieskovan
  • Robert Damoiseaux
  • Roger S Lo
  • Antoni Ribas
چکیده

PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter. PD-L2 responded equally to interferon beta and gamma and is regulated through both IRF1 and STAT3, which bind to the PD-L2 promoter. Analysis of biopsy specimens from patients with melanoma confirmed interferon signature enrichment and upregulation of gene targets for STAT1/STAT2/STAT3 and IRF1 in anti-PD-1-responding tumors. Therefore, these studies map the signaling pathway of interferon-gamma-inducible PD-1 ligand expression.

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عنوان ژورنال:
  • Cell reports

دوره 19 6  شماره 

صفحات  -

تاریخ انتشار 2017