PXD014165 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma |
Description | The accessibility of cell surface proteins makes them tractable for cancer immunotherapy, but identifying suitable targets remains challenging, and resistance to treatment is common. Technical difficulties precluding the use of whole cell proteomic approaches to characterize cell surface proteins include low abundance, hydrophobicity, and a lack of protease cleavage sites. Furthermore, neither whole-cell proteomic nor transcriptomic data can accurately quantify protein expression at the plasma membrane. Resistance to immunotherapies is commonly mediated by downregulation of the target protein, a particular problem when immunotherapies fail to inhibit a specific biological pathway. Here we have used plasma membrane profiling of primary human myeloma cells to identify an unprecedented number of cell surface proteins and quantify for the first time the entire cell surface proteome of a primary cancer. This approach revealed a novel therapeutic target, SEMA4A, which we potently and selectively targeted with an antibody-drug conjugate in vitro and in vivo. Reduction of SEMA4A expression resulted in marked impairment of myeloma cell growth in vitro, indicating that myeloma cells cannot downregulate SEMA4A to avoid detection. Our data therefore reveal not only a novel myeloma target but provide an exemplar of a top-down approach from the unbiased characterization of a cancer cell surface proteome to novel immunotherapeutic target. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-08 |
AnnouncementXML | Submission_2024-10-08_11:13:33.622.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD014165 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | James Williamson |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex; Oxidation; Carbamidomethyl |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-06-07 01:14:47 | ID requested | |
⏵ 1 | 2024-10-08 11:13:34 | announced | |
Publication List
Keyword List
submitter keyword: TMT, Plasms membrane profiling,Myeloma, Immunotherapy |
Contact List
Mike Chapman |
contact affiliation | Department of Haematology, University of Cambridge |
contact email | mac54@cam.ac.uk |
lab head | |
James Williamson |
contact affiliation | University of Cambridge |
contact email | jcw76@cam.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD014165
- Label: PRIDE project
- Name: Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma