دورية أكاديمية
Targeting the NAT10/NPM1 axis abrogates PD-L1 expression and improves the response to immune checkpoint blockade therapy
| العنوان: | Targeting the NAT10/NPM1 axis abrogates PD-L1 expression and improves the response to immune checkpoint blockade therapy |
|---|---|
| المؤلفون: | Ge Qin, Fan Bai, Huabin Hu, Jianwei Zhang, Weixiang Zhan, Zehua Wu, Jianxia Li, Yang Fu, Yanhong Deng |
| المصدر: | Molecular Medicine, Vol 30, Iss 1, Pp 1-16 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Therapeutics. Pharmacology LCC:Biochemistry |
| مصطلحات موضوعية: | NPM1, NAT10, PD-L1, Immunotherapy, Remodelin, Therapeutics. Pharmacology, RM1-950, Biochemistry, QD415-436 |
| الوصف: | Abstract Background PD-1/PD-L1 play a crucial role as immune checkpoint inhibitors in various types of cancer. Although our previous study revealed that NPM1 was a novel transcriptional regulator of PD-L1 and stimulated the transcription of PD-L1, the underlying regulatory mechanism remains incompletely characterized. Methods Various human cancer cell lines were used to validate the role of NPM1 in regulating the transcription of PD-L1. The acetyltransferase NAT10 was identified as a facilitator of NPM1 acetylation by coimmunoprecipitation and mass spectrometry. The potential application of combined NAT10 inhibitor and anti-CTLA4 treatment was evaluated by an animal model. Results We demonstrated that NPM1 enhanced the transcription of PD-L1 in various types of cancer, and the acetylation of NPM1 played a vital role in this process. In particular, NAT10 facilitated the acetylation of NPM1, leading to enhanced transcription and increased expression of PD-L1. Moreover, our findings demonstrated that Remodelin, a compound that inhibits NAT10, effectively reduced NPM1 acetylation, leading to a subsequent decrease in PD-L1 expression. In vivo experiments indicated that Remodelin combined with anti-CTLA-4 therapy had a superior therapeutic effect compared with either treatment alone. Ultimately, we verified that the expression of NAT10 exhibited a positive correlation with the expression of PD-L1 in various types of tumors, serving as an indicator of unfavorable prognosis. Conclusion This study suggests that the NAT10/NPM1 axis is a promising therapeutic target in malignant tumors. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1528-3658 |
| Relation: | https://doaj.org/toc/1528-3658 |
| DOI: | 10.1186/s10020-024-00780-4 |
| URL الوصول: | https://doaj.org/article/24db86fb83764869a361d84c24d9963e |
| رقم الأكسشن: | edsdoj.24db86fb83764869a361d84c24d9963e |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 15283658 |
|---|---|
| DOI: | 10.1186/s10020-024-00780-4 |