Sokotrasterol Sulfate Suppresses IFN-γ-Induced PD-L1 Expression by Inhibiting JAK Activity.
J Nat Prod
; 87(4): 713-721, 2024 04 26.
Article
em En
| MEDLINE
| ID: mdl-38417168
ABSTRACT
PD-1/PD-L1 monoclonal antibodies exhibit promising therapeutic effectiveness in multiple cancers. However, developing a simple and efficient non-antibody treatment strategy using the PD-1/PD-L1 signaling pathway still remains challenging. In this study, we developed a flow cytometry assay to screen bioactive compounds with PD-L1 inhibitory activity. A total of 409 marine natural products were screened, and sokotrasterol sulfate (SKS) was found to efficiently suppress the IFN-γ-induced PD-L1 expression. SKS sensitizes the tumor cells to antigen-specific T-cell killing in the T cell-tumor cell coculture system. Mechanistically, SKS directly targeted Janus kinase (JAK) to inhibit the downstream activation of signal transducer and activator of transcription (STAT) and the subsequent transcription of PDL1. Our findings highlight the immunological role of SKS that may act as a basis for a potential immunotherapeutic agent.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interferon gama
/
Janus Quinases
/
Antígeno B7-H1
Limite:
Humans
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2024
Tipo de documento:
Article