PXD016582

PXD016582 is an original dataset announced via ProteomeXchange.

Title	Intra-patient clonal diversity in HLA class I peptide ligand presentation
Description	Tumor heterogeneity results from clonal diversity and evolutionary selection, and is a major cause of therapeutic resistance. Immunotherapy may exploit alternative vulnerabilities of drug resistant cells, and tumor-specific HLA peptide ligands on the cell surface are promising leads to invoke such targeted anti-tumor responses. In this work, we investigate the variability in HLA class I peptide presentation between tumor cells of the same patient, as differential ligand presentation could impact the efficacy of immunological interventions. By organoid amplification, we modeled single-cell level heterogeneity in a MSI- colorectal cancer patient, and directly correlated clonal tumor proteomes with the respective ligandomes. With deep comparative proteome profiling and sensitive detection of >7000 peptide ligands from each tumor organoid line, we found tumor-surface peptide presentation to be largely uncoupled from the steady-state protein abundance. Within the small minority of tumor-specific ligands (~3%), source proteins needed for DNA damage sensing and repair, and tumor suppression were prominently featured, leading us to speculate that such peptides may be consistently presented, as degradative byproducts of intended silencing. While clone-specific differences in peptide presentation were observed, inter-clone variability was also highly prevalent (15-25%). Collectively, these illustrate the heterogeneous peptide presentation landscape even within one individual, and hint that a multi-peptide vaccination approach against highly conserved tumor suppressors may be a viable option in patients with low tumor-mutational burden.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:14:07.762.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Demmers
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-04 03:33:34	ID requested
1	2020-10-26 00:41:37	announced
2	2022-02-13 16:37:50	announced	2022-02-14: Updated project metadata.
⏵ 3	2024-10-22 05:14:11	announced	2024-10-22: Updated project metadata.

10.1038/s41467-020-19142-9;

Demmers LC, Kretzschmar K, Van Hoeck A, Bar-Epra, ï, m YE, van den Toorn HWP, Koomen M, van Son G, van Gorp J, Pronk A, Smakman N, Cuppen E, Clevers H, Heck AJR, Wu W, Single-cell derived tumor organoids display diversity in HLA class I peptide presentation. Nat Commun, 11(1):5338(2020) [pubmed]

ProteomeXchange project tag: Human Immuno-Peptidome Project (HUPO-HIPP) (B/D-HPP), EPIC-XS, Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: HLA class I peptide ligands

colorectal cancer

tumor heterogeneity

patient-derived organoids

mass spectrometry

affinity proteomics

Wei Wu
contact affiliation	Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands
contact email	w.wu1@uu.nl
lab head
Laura Demmers
contact affiliation	Utrecht University
contact email	l.c.demmers@uu.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/2020/10/PXD016582

PRIDE project URI

• PRIDE
  1. PXD016582
     1. Label: PRIDE project
     2. Name: Intra-patient clonal diversity in HLA class I peptide ligand presentation