| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 19, Iss 6, Pp 1189-1201 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2017.04.031 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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