PXD044115 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Engineered immunomodulatory extracellular vesicles derived from epithelial cells acquire capacity for positive and negative T cell co-stimulation in cancer and autoimmunity. |
Description | Extracellular vesicles (EVs) are generated by all cells and systemic injection of allogenic EVs derived from epithelial or mesenchymal cells into humans and immunocompetent mice do not elicit any immune response despite the presence of ~1,200 proteins. Nevertheless, EVs from immune cells are purported to play a role in immune regulation associated with cancer and other diseases. To specifically address whether epithelial cells derived EVs can be modified to inherently acquire a capacity to induce immune response, we engineered epithelial 293T EVs to harbor the immunomodulatory CD80, OX40L and PD-L1 molecules. We demonstrated abundant levels of these proteins on the engineered EVs, without causing major morphological and molecular alterations in the donor cells and their shed EVs. Functionally, the engineered EVs efficiently elicit positive and negative T cells co-stimulation in both human and murine T cells ex vivo. The systemic administration of OX40L-containing EVs promotes anti-tumor immunity, whereas PD-L1-containing EVs suppresses T cell-mediated anti-tumor responses. Conversely, OX40L EVs worsen the progression of auto-immune hepatitis, while PD-L1 EVs ameliorate it. Moreover, OX40L EVs synergize with anti-CTLA-4 to delay tumor growth and extend the survival of melanoma-bearing mice. Taken together, our work provides evidence that while epithelial cells derived EVs are immunologically inert when systemically infused in large numbers, the same EVs can be engineered to induce immune response with translational potential to modulate T cell functions in pathological settings. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-08 |
AnnouncementXML | Submission_2025-05-08_08:12:05.033.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Sergio Lilla |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-07-26 11:51:32 | ID requested | |
⏵ 1 | 2025-05-08 08:12:05 | announced | |
Publication List
10.1021/acsnano.4c09688; |
Luo X, Kugeratski FG, Dowlatshahi DP, Sugimoto H, Arian KA, Fan Y, Huang L, Wills D, Lilla S, Hodge K, Zanivan SR, LeBleu VS, McAndrews KM, Kalluri R, Engineered Immunomodulatory Extracellular Vesicles from Epithelial Cells with the Capacity for Stimulation of Innate and Adaptive Immunity in Cancer and Autoimmunity. ACS Nano, 19(5):5193-5216(2025) [pubmed] |
Keyword List
submitter keyword: T cell function, Cancer,Extracellular vesicles, Immune regulation |
Contact List
Sara Rossana Zanivan |
contact affiliation | CRUK - Beatson Institute for Cancer Research - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom |
contact email | s.zanivan@beatson.gla.ac.uk |
lab head | |
Sergio Lilla |
contact affiliation | Proteomics |
contact email | s.lilla@beatson.gla.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD044115 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044115
- Label: PRIDE project
- Name: Engineered immunomodulatory extracellular vesicles derived from epithelial cells acquire capacity for positive and negative T cell co-stimulation in cancer and autoimmunity.