PXD060641-1

PXD060641 is an original dataset announced via ProteomeXchange.

Title	An oncogenic SUMO program restricts the targetable cancer immunopeptidome
Description	A balanced SUMOylation equilibrium safeguards the functional anti-tumor immune response. Oncogene activation drives SUMOylation, rendering aberrant SUMOylation a hallmark of cancer. To delineate the impact of activated SUMOylation on the tumor-immune synapse, we applied HLA class-I-targeted ligandomics and identified a function of activated SUMOylation in restricting the immunopeptidome landscape. Importantly, aberrant SUMOylation suppressed a unique HLA-I peptide and oncoprotein-derived neoepitope repertoire, enabling cancer cells to evade T cell immune surveillance. Mechanistically, SUMOylation impaired the immunoproteasome constitution and proteolytic activity, thus limiting the diversity of the peptide landscape. Additionally, SUMOylation altered TAP1 transporter binding preferences, thereby mimicking viral immune evasion strategies. As an actionable application, pharmacological inhibition of SUMOylation unmasked the targetable immunopeptidome and enhanced the tumor cell susceptibility to T cell killing. These findings highlight SUMOylation as a critical regulator of the adaptive antitumor immune response. We propose SUMO inhibition as a rational strategy to enhance immunogenic peptide presentation for more effective cancer immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2026-04-06
AnnouncementXML	Submission_2026-04-05_17:32:27.148.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-10 08:53:55	ID requested
⏵ 1	2026-04-05 17:32:28	announced

10.1002/advs.202511449;

Demel UM, Meurer A, Zaghla BKQ, Atay B, Steiert D, Hummel LV, Isaakidis K, Zang C, Korenkov M, Schielin M, Yousefian S, Mecklenbr, ä, uker S, Kirchner M, Haas S, Busse A, Mertins P, M, ü, ller S, Wirth M, Klatt MG, Keller U, Aberrant SUMOylation Restricts the Targetable Cancer Immunopeptidome. Adv Sci (Weinh), 13(17):e11449(2026) [pubmed]

submitter keyword: Human, SUMO, IMMUNOPEPTIDOME, MHC-I, ANTIGEN PRESENTATION, CANCER IMMUNOTHERAPY, Phosphoproteome

Philipp Mertins
contact affiliation	Core Unit Proteomics, Berlin Institute of Health at Charité-Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany
contact email	philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
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/PXD060641

PRIDE project URI

• PRIDE
  1. PXD060641
     1. Label: PRIDE project
     2. Name: An oncogenic SUMO program restricts the targetable cancer immunopeptidome