PXD028309

PXD028309 is an original dataset announced via ProteomeXchange.

Title	Discovery of tumor-specific antigens in colorectal cancer
Description	Colorectal cancer is the second leading cause of cancer death worldwide, and the incidence of this disease is expected to increase as global socioeconomic changes occur. Immune checkpoint inhibition therapy is effective in treating a minority of colorectal cancer tumors; however, microsatellite stable tumors do not respond well to this treatment. Emerging cancer immunotherapeutic strategies aim to activate a cytotoxic T cell response against tumor-specific antigens, presented exclusively at the cell surface of cancer cells. These antigens are rare and are most effectively identified with a mass spectrometry-based approach, which allows the direct sampling and sequencing of these peptides. While the few tumor-specific antigens identified to date derived from coding regions of the genome, recent findings indicate that a large proportion of tumor-specific antigens originate from allegedly noncoding regions. Here, we employed a novel proteogenomic approach to identify tumor antigens in a collection of colorectal cancer-derived cell lines and biopsy samples consisting of matched tumor and normal adjacent tissue. The generation of personalized cancer databases paired with mass spectrometry analyses permitted the identification of more than 30 000 unique MHC I-associated peptides. We identified 19 putative tumor-specific antigens in both microsatellite stable and unstable tumors, over two-thirds of which were derived from non-coding regions. Many of these peptides were derived from source genes known to be involved in colorectal cancer progression, suggesting that antigens from these genes could have therapeutic potential in a wide range of tumors. These findings could benefit the development of T cell-based vaccines, in which T cells are primed against these antigens to target and eradicate tumors. Such a vaccine could be used in tandem with existing immune checkpoint inhibition therapies, to bridge the gap in treatment efficacy across subtypes of colorectal cancer with varying prognoses.
HostingRepository	PRIDE
AnnounceDate	2022-04-13
AnnouncementXML	Submission_2022-04-13_03:33:34.565.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028309
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Courcelles Mathieu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:21:04	ID requested
⏵ 1	2022-04-13 03:33:35	announced

Cleyle J, Hardy MP, Minati R, Courcelles M, Durette C, Lanoix J, Laverdure JP, Vincent K, Perreault C, Thibault P, Immunopeptidomic analyses of colorectal cancers with and without microsatellite instability. Mol Cell Proteomics, 21(5):100228(2022) [pubmed]

submitter keyword: Colorectal cancer, LC-MSMS, MHC class I, immunopeptidome

Pierre Thibault
contact affiliation	Institute for Research in Immunology and Cancer, Department of Biochemistry, Department of Chemistry, Université de Montréal, Québec, Canada H3T 1J4
contact email	pierre.thibault@umontreal.ca
lab head
Courcelles Mathieu
contact affiliation	IRIC
contact email	mathieu.courcelles@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028309
     1. Label: PRIDE project
     2. Name: Discovery of tumor-specific antigens in colorectal cancer