PXD061196

PXD061196 is an original dataset announced via ProteomeXchange.

Title	Aberrant SUMOylation 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. Further, 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 anti-tumor immune response. We propose SUMO inhibition as a strategic approach to enhance immunogenic peptide presentation, thereby improving the efficacy of cancer immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2026-01-25
AnnouncementXML	Submission_2026-01-25_14:57:12.197.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD061196
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Martin Klatt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	cysteinylation (disulfide with free L-cysteine); phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-25 16:06:06	ID requested
⏵ 1	2026-01-25 14:57:12	announced

10.6019/PXD061196;

10.1002/ADVS.202511449;

submitter keyword: SUMOylation,Immunpeptidome

Martin Klatt
contact affiliation	Charité-University Medicine Berlin
contact email	martin.klatt@charite.de
lab head
Martin Klatt
contact affiliation	Charite - University Medicine Berlin
contact email	martin.g.klatt@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061196
     1. Label: PRIDE project
     2. Name: Aberrant SUMOylation restricts the targetable cancer immunopeptidome