PPARα phosphorylation regulates colorectal tumor immune escape.
J Biol Chem
; 300(7): 107447, 2024 Jul.
Article
en En
| MEDLINE
| ID: mdl-38844134
ABSTRACT
A high level of PD-L1 in cancer cells promotes tumor immune escape and inhibits tumor immunotherapy. Although PD-L1 gene expression is upregulated by multiple pathways, its gene transcriptional repression is still unclear. Here we found that loss of PPARα, one of the peroxisome-proliferator-activated receptors (PPARs) family members, promoted colorectal tumor immune escape. Mechanistically, PPARα directly bound to the PD-L1 promoter resulting in its gene transcriptional repression, which in turn increased T cell activity, and PPARα agonist enhanced this event. However, ERK induced PPARα-S12 phosphorylation leading to blockade of PPARα-mediated PD-L1 transcriptional repression, and the combination of ERK inhibitor with PPARα agonist significantly inhibited tumor immune escape. These findings suggest that the ERK-PPARα pathway inhibited PD-L1 gene transcriptional repression and promoted colorectal tumor immune escape.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Escape del Tumor
/
PPAR alfa
/
Antígeno B7-H1
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2024
Tipo del documento:
Article