Reference - Detail
| RRC ID | 86414 |
|---|---|
| Author | 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. |
| Title | Statins attenuate PD-L1 sorting to small extracellular vesicles dependent on ubiquitin-like 3 modification. |
| Journal | 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. |
| Volume | 15(1) |
| Pages | 43802 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 32 |
| Altmetric score changes over past 6months | 53.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |