PXD076608

PXD076608 is an original dataset announced via ProteomeXchange.

Title	Kinase inhibition rewires the HLA-I immunopeptidome in Chronic Myeloid Leukemia
Description	Antileukemia immunity is essential for disease control and maintaining treatment-free remission in chronic myeloid leukemia (CML). Immunotherapeutic approaches hold significant promise for enhancing immune-mediated disease control. However, successful immunotherapy relies on identifying CML-associated antigens and achieving robust antigen presentation. Protein kinases are central regulators of signaling, and protein turnover, influencing which peptides are processed and presented on HLA molecules. Indeed, previous works with CDK4/6 or MEK inhibitors showed that kinases influence immune recognition of cancer cells. However, the molecular mechanisms underlying the modulation of the immunopeptidome by kinases inhibitors treatment remained unclear. Here, we investigated whether pharmacological inhibition of key kinases, including BCR-ABL, JNK and LCK, could be leveraged to reshape the immunopeptidome of CML cells, enhancing the exposure of specific tumor-associated antigens. By employing high-sensitive mass spectrometry (MS)–based immunopeptidomics, we quantified more than 20,000 HLA-I peptides. Pharmacological suppression of LCK, JNK and BCR-ABL drastically remodels the antigen landscape, impacting the exposure of about 4,000 HLA-I ligands. By integrating immunopeptidomics, phospho-immunopeptidomics, and proteomic, our study revealed three complementary molecular mechanisms of kinase-dependent antigen control: direct phosphorylation of HLA-I peptides (i), modulation of source protein stability (ii), and control of transcription factors governing antigen expression (iii). Moreover, comparative HLA ligandome analysis of benign hematological specimens and CML primary samples identified a panel of about 90 frequently presented CML-exclusive peptides, whose presentation can be significantly increased by LCK and JNK inhibition. Our study establishes a framework to rationally combine kinase inhibitors with immunotherapies to enhance antigen visibility and improve antileukemic immunity.
HostingRepository	PRIDE
AnnounceDate	2026-06-01
AnnouncementXML	Submission_2026-05-31_16:09:00.825.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maria Wahle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue
Instrument	timsTOF Ultra

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-04 12:13:24	ID requested
⏵ 1	2026-05-31 16:09:01	announced

10.1016/j.isci.2026.115944;

Venafra V, Wahle M, Massacci G, Bica V, Chiusolo P, Mougiakakos D, Boettcher M, Fischer T, Perfetto L, Mann M, Sacco F, Kinase inhibition rewires the HLA-I immunopeptidome in chronic myeloid leukemia. iScience, 29(6):115944(2026) [pubmed]

submitter keyword: Kinase inhibitors,Immunopeptidomics, proteomics, CML

Francesca Sacco
contact affiliation	Department of Biology, University of Rome Tor Vergata, Rome, Italy Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Naples, Italy
contact email	francesca.sacco@uniroma2.it
lab head
Maria Wahle
contact affiliation	Max-Planck-Institute of Biochemistry
contact email	wahle@biochem.mpg.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/2026/06/PXD076608

PRIDE project URI

• PRIDE
  1. PXD076608
     1. Label: PRIDE project
     2. Name: Kinase inhibition rewires the HLA-I immunopeptidome in Chronic Myeloid Leukemia