PXD014017 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Immunopeptidomics of colorectal cancer organoids |
Description | Background: Patient derived organoids (PDOs) can be established from colorectal cancers as in vitro models to interrogate cancer biology and its clinical relevance. We applied mass spectrometry (MS) immunopeptidomics to investigate neoantigen presentation and whether this can be augmented through interferon gamma (IFN) or MEK-inhibitors. Methods: Four PDOs from chemotherapy refractory and one from a treatment naïve CRC were expanded to replicates with 100 million cells each, and HLA class I and class II peptide ligands were analysed by MS. Results: We identified an average of 9,936 unique peptides per PDO which compares favourably against published immunopeptidomics studies, suggesting high sensitivity. Loss of heterozygosity of the HLA locus was associated with low peptide diversity in one PDO. Peptides from genes without detectable expression by RNA-sequencing were rarely identified by MS. Only 3 out of 612 non-silent mutations encoded for neoantigens that were detected by MS. Treatment of four PDOs with IFN upregulated HLA class I expression and qualitatively changed the immunopeptidome, with increased presentation of IFN-inducible genes. HLA class II presented peptides increased on average 16-fold with IFN treatment. MEK-inhibitor treatment showed no consistent effect on class I or II HLA expression or the peptidome. Importantly, no additional HLA class I or II presented neoantigens became detectable with any treatment. Conclusions: Only 3 out of 612 non-synonymous mutations encoded for neoantigens that were detectable by MS. Although MS has sensitivity limits and biases, and likely underestimated the true neoantigen burden, this established a lower bound of the percentage of non-silent mutations that encode for presented neoantigens, which may be as low as 0.5%. This could be a reason for the poor responses of non-hypermutated CRCs to immune checkpoint inhibitors. MEK-inhibitors recently failed to improve checkpoint-inhibitor efficacy in CRC and the observed lack of HLA upregulation or improved peptide presentation may explain this. |
HostingRepository | PRIDE |
AnnounceDate | 2019-11-27 |
AnnouncementXML | Submission_2019-11-27_12:04:47.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Michal Bassani-Sternberg |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-05-27 00:56:10 | ID requested | |
⏵ 1 | 2019-11-27 12:04:49 | announced | |
Publication List
Newey A, Griffiths B, Michaux J, Pak HS, Stevenson BJ, Woolston A, Semiannikova M, Spain G, Barber LJ, Matthews N, Rao S, Watkins D, Chau I, Coukos G, Racle J, Gfeller D, Starling N, Cunningham D, Bassani-Sternberg M, Gerlinger M, Immunopeptidomics of colorectal cancer organoids reveals a sparse HLA class I neoantigen landscape and no increase in neoantigens with interferon or MEK-inhibitor treatment. J Immunother Cancer, 7(1):309(2019) [pubmed] |
Keyword List
ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project |
curator keyword: Biomedical |
submitter keyword: colorectal cancer, organoids, immunopeptidomics, mass spectrometry |
Contact List
Michal Bassani-Sternberg |
contact affiliation | Department of oncology UNIL CHUV Ludwig Institute for Cancer Research Lausanne |
contact email | michal.bassani@chuv.ch |
lab head | |
Michal Bassani-Sternberg |
contact affiliation | UNIL/CHUV |
contact email | michal.bassani@chuv.ch |
dataset submitter | |
Full Dataset Link List
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/2019/11/PXD014017 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD014017
- Label: PRIDE project
- Name: Immunopeptidomics of colorectal cancer organoids