Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression.
Biomed Pharmacother
; 170: 116078, 2024 Jan.
Article
in En
| MEDLINE
| ID: mdl-38159375
ABSTRACT
PD-L1-mediated immune escape plays an important role in cancer development and progression. Targeting PD-L1 is consider to be an attractive approach for cancer treatment. PD-L1 is a heavily N-linked glycosylated protein, and the glycosylation of PD-L1 is essential for its ability to interact with its receptor PD-1 to mediate immune suppression. In the present study, we demonstrated for the first time that delta-tocotrienol (δ-T3) not any of the other forms of vitamin E was able to disrupt PD-L1 glycosylation mechanistically associated with the suppression of TCF4-STT3a/STT3b axis. The inhibition of PD-L1 glycosylation by δ-T3 resulted in the decrease of PD-L1 expression and its exosomal secretion, leading to the reduction of PD-L1 and PD-1 interaction, and reversing PD-L1-mediated immune suppression, which in turn contributed to the inhibitory effect on tumor growth. The findings of the present study provide a novel mechanistic interpretation for the superior anticancer activity of δ-T3 among 8 isomers of the vitamin E.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
B7-H1 Antigen
/
Programmed Cell Death 1 Receptor
Language:
En
Journal:
Biomed Pharmacother
Year:
2024
Document type:
Article
Country of publication:
FR
/
FRANCE
/
FRANCIA
/
FRANÇA