Skip to main content
eScholarship
Open Access Publications from the University of California

UCLA

UCLA Previously Published Works bannerUCLA

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

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

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View