PXD064698-1

PXD064698 is an original dataset announced via ProteomeXchange.

Title	Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma
Description	PD-L1 functions as a co-inhibitory checkpoint ligand constraining anti-tumor immunity by binding to PD-1 on immune cells. Although antibody blockade therapy displays clear therapeutic responses, it is not effective in all cancer patients, indicating modulation by other factors. We applied cell surface proximity biotinylation combined with mass spectrometry in melanoma cells to identify novel proteins regulating PD-L1 function. Our findings reveal that membrane organizing protein Tetraspanin-4 (TSPAN4) interacts with PD-L1, where both proteins colocalize on migrasomes and retraction fibers. We demonstrate that TSPAN4 negatively affects PD-L1 protein levels and inhibits PD-L1 lateral mobility on the plasma membrane. TSPAN4 knockdown results in a reduced PD-L1 degradation rate, and enhanced PD-L1 interaction with CMTM6 as the molecular mechanism. Consequently, increased PD-L1 levels in TSPAN4 knockdown melanoma cells leads to enhanced PD-1 binding, and more efficient immune checkpoint blockade through inhibition of T cell responses. This study identifies TSPAN4 as a negative regulator of PD-L1 at the cell surface of melanoma cells, suggesting that TSPAN4 may represent a novel target for improving immune checkpoint therapy in cancer patients.
HostingRepository	PRIDE
AnnounceDate	2026-01-16
AnnouncementXML	Submission_2026-01-16_02:59:03.423.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guido van Mierlo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-05 11:34:07	ID requested
⏵ 1	2026-01-16 02:59:05	announced

10.1002/1878-0261.70182;

Franken GA, Abel Gutierrez A, van Rossum I, Spruijt CG, Vermeulen M, van Mierlo G, Scheijen B, van Spriel AB, Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma. Mol Oncol, ():(2026) [pubmed]

submitter keyword: TSPAN4,PD-L1,melanoma,surface proximity biotinylation

Guido van Mierlo
contact affiliation	Department of Medical BioSciences, Radboud Institute for Medical Innovation, Radboudumc, Nijmegen, The Netherlands
contact email	Guido.vanMierlo@radboudumc.nl
lab head
Guido van Mierlo
contact affiliation	Radboudumc
contact email	guido.vanmierlo@radboudumc.nl
dataset submitter

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/2026/01/PXD064698

PRIDE project URI

• PRIDE
  1. PXD064698
     1. Label: PRIDE project
     2. Name: Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma