| RRC ID |
86414
|
| 著者 |
Ageta H, Shimada Y, Nagaoka T, Takenaka K, Yoshioka Y, Konno K, Amemiya R, Nagase K, Hitachi K, Onouchi T, Watanabe M, Ochiya T, Tsuchida K.
|
| タイトル |
Statins attenuate PD-L1 sorting to small extracellular vesicles dependent on ubiquitin-like 3 modification.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Small extracellular vesicles (sEVs) mediate cell-to-cell communication by carrying RNAs and proteins. Ubiquitin-like 3 (UBL3) functions as a posttranslational modification factor, regulating protein sorting to sEVs. Programmed cell death ligand 1 (PD-L1) binds to programmed cell death 1 (PD-1) on immune cells, suppressing their function. Although immune checkpoint inhibitors, anti-PD-L1 and anti-PD-1 antibodies, have improved cancer treatment, efficacy remains limited (~ 25%). Per recent studies, PD-L1-containing sEVs are elevated in cancer patients, contributing to impaired immunotherapy responses. Herein, we discovered that PD-L1 is modified by UBL3 and that its sorting to sEVs is regulated by UBL3. Furthermore, we found that statins, commonly prescribed for hypercholesterolemia, inhibit UBL3 modification, thereby reducing PD-L1 sorting to sEVs. Among patients with a high tumor proportion score, serum levels of PD-L1-containing sEVs were significantly lower in those using statins. Consistently, bioinformatic analysis revealed that UBL3 and PD-L1 expression levels affect lung cancer survival. Integrating statins into existing combination therapies may therefore offer a promising strategy to enhance immunotherapy efficacy.
|
| 巻・号 |
15(1)
|
| ページ |
43802
|
| 公開日 |
2025-12-15
|
| DOI |
10.1038/s41598-025-27789-x
|
| PII |
10.1038/s41598-025-27789-x
|
| PMID |
41398009
|
| PMC |
PMC12706078
|
| MeSH |
B7-H1 Antigen* / metabolism
Cell Line, Tumor
Extracellular Vesicles* / drug effects
Extracellular Vesicles* / metabolism
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
Lung Neoplasms* / drug therapy
Lung Neoplasms* / metabolism
Lung Neoplasms* / pathology
Protein Processing, Post-Translational / drug effects
Protein Transport / drug effects
Ubiquitins* / genetics
Ubiquitins* / metabolism
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
