PXD069094

PXD069094 is an original dataset announced via ProteomeXchange.

Title	Immunopeptidomic analyses - HLA Export by Melanoma Cells Decoys Cytotoxic T Cells to Promote Immune Evasion
Description	While melanoma cells often express a high burden of mutated proteins, the infiltration of reactive T cells rarely results in tumor-eradicating immunity. We discovered that large extracellular vesicles, known as melanosomes, secreted by melanoma cells are decorated with MHC molecules that stimulate CD8+ T cells through their T-cell receptor (TCR), causing T cell dysfunction and apoptosis. Immunopeptidomic and TCR-seq analyses revealed that these melanosomes carry MHC-bound-Tumor-Associate- Antigens with higher affinity and immunogenicity, which compete with their tumor cell of origin for direct TCR–MHC interactions. Analysis of biopsies from melanoma patients confirmed that melanosomes trap infiltrating lymphocytes, induce partial activation, and decrease CD8+ T cell cytotoxicity. Inhibition of melanosome secretion in vivo significantly reduced tumor immune evasion. These findings suggest that MHC export protects melanoma from the cytotoxic effects of T cells. Our study highlights a novel immune evasion mechanism and proposes a therapeutic avenue to enhance tumor immunity.
HostingRepository	PRIDE
AnnounceDate	2026-04-19
AnnouncementXML	Submission_2026-04-19_02:37:50.524.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chen Weller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF; ultraflex

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-02 12:15:03	ID requested
⏵ 1	2026-04-19 02:37:51	announced

10.1016/j.cell.2025.11.020;

Chemla Y, Itzhaki O, Melamed S, Weller C, Sade Y, Manich P, Reshef K, Xenidis N, Maliah A, Levy G, Parikh R, Bartok O, Levy O, Tal I, Aziel G, Nissani A, Yunger S, Likonen D, Kliminsky V, Golan T, Capron C, Ace V, Levy R, Rasoulouniriana D, Eyal Z, Barzilay Y, Balaban R, Khateeb A, Khosravi R, Grau A, Ziv T, Greenberg P, Netanely D, Vaknin H, Wu X, Amitay Y, Brenner R, Mart, í, nez G, ó, mez JM, Hershkovitz D, Yardeni T, Zemser-Werner V, Kobiler O, Friedmann Y, Bassan D, Shamir R, Eisenbach L, Santana-Magal N, Milyavsky M, Eisenberg G, Keren L, Cohen M, Gur D, Barak B, Lotem M, Sprinzak D, Greenberger S, Fisher D, Besser MJ, Khaled M, Close P, Shapira R, Apcher S, Madi A, Levesque MP, Rapino F, Carmi Y, Parikh S, Samuels Y, Levy C, HLA export by melanoma cells decoys cytotoxic T cells to promote immune evasion. Cell, 189(1):233-251.e29(2026) [pubmed]

submitter keyword: Melanoma, Melanosomes, Immunopeptidome

Yardena Samuels
contact affiliation	Molecular Cell Biolody, Weizmann Institute of Science.
contact email	yardena.samuels@weizmann.ac.il
lab head
Chen Weller
contact affiliation	Yardena Samuels lab, Weizmann Institute of Science
contact email	chen.weller@weizmann.ac.il
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/2026/04/PXD069094

PRIDE project URI

• PRIDE
  1. PXD069094
     1. Label: PRIDE project
     2. Name: Immunopeptidomic analyses - HLA Export by Melanoma Cells Decoys Cytotoxic T Cells to Promote Immune Evasion