EP300 restores the glycolytic activity and anti-tumor function of CD8+ cytotoxic T cells in nasopharyngeal carcinoma.
iScience
; 27(2): 108957, 2024 Feb 16.
Article
in En
| MEDLINE
| ID: mdl-38333692
ABSTRACT
Competition for glucose may metabolically limit T cells during cancer progression. This study shows that culturing in the condition medium (CM) of NPC c6661 cells restricted glycolytic and immune activities of CD8+ T cells. These cells also exhibited limited tumor-eliminating effects in mouse xenograft tumor models. Glucose supplementation restored glycolysis and immune activity of CD8+ T cells in vitro and in vivo by rescuing the expression of E1A binding protein p300 (EP300). EP300 upregulated bromodomain PHD finger transcription factor (BPTF) expression by catalyzing H3K27ac modification, and BPTF further activated AT-rich interaction domain 1A (ARID1A) transcription. Either BPTF or ARID1A knockdown in CD8+ T cells reduced their glycolytic activity, decreased the secretion of cytotoxic molecules, and blocked the tumor-killing function in mice. Overall, this study demonstrates that EP300 restores the glycolytic and anti-tumor activities of CD8+ T cells in the glucose restriction condition in NPC through the BPTF/ARID1A axis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
IScience
Year:
2024
Document type:
Article