PXD023044

PXD023044 is an original dataset announced via ProteomeXchange.

Title	IFNγ modulates the immunopeptidome of triple negative breast cancer cells by enhancing and diversifying antigen processing and presentation.
Description	Peptide vaccination remains a viable approach to induce T-cell mediated killing of tumours. To identify potential T-cell targets for Triple-Negative Breast Cancer (TNBC) vaccination, we examined the effect of the pro-inflammatory cytokine interferon-γ (IFNγ) on the transcriptome, proteome and immunopeptidome of the TNBC cell line MDA-MB-231. Using high resolution mass spectrometry, we identified a total of 84,131 peptides from 9,647 source proteins presented by human leukocyte antigen (HLA)-I and HLA-II alleles. Treatment with IFNγ resulted in a remarkable remoulding of the immunopeptidome, with only a 34% overlap between untreated and treated cells across the HLA-I immunopeptidome, and expression of HLA-II only on treated cells. IFNγ increased the overall number, diversity and abundance of the immunopeptidome, as well as the proportion of coverage of source antigens. The suite of peptides displayed under conditions of IFNγ treatment included many known tumour associated antigens, with the HLA-II repertoire sampling 265 breast cancer associated antigens absent from those sampled by HLA-I. Quantitative analysis of the transcriptome (10,248 transcripts) and proteome (6783 proteins) of these cells revealed 229 proteins and transcripts were commonly differentially expressed, most of which involved in downstream targets of IFNγ signalling including components of the antigen processing machinery such as tapasin and HLA. However, these changes in protein expression did not explain the dramatic modulation of the immunopeptidome following IFNγ treatment. These results demonstrate the high degree of plasticity in the immunopeptidome TNBC cells following cytokine stimulation and provide evidence that under pro-inflammatory conditions a greater variety of HLA-I and HLA-II vaccine targets are unveiled to the immune system. This has important implications for the development of personalised cancer vaccination strategies.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:51:52.444.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD023044
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pouya Faridi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-10 01:36:04	ID requested
1	2021-05-12 20:48:47	announced
⏵ 2	2023-11-14 08:51:53	announced	2023-11-14: Updated project metadata.

10.6019/PXD023044;

submitter keyword: HLA,Breast cancer, Immunopeptidomics

Anthony Purcell
contact affiliation	Deputy Head (Research), Department of Biochemistry and Molecular Biology Head Immunoproteomics Laboratory Infection and Immunity Program Room 214, level 2, 15 Innovation Walk Monash Biomedicine Discovery Institute Monash University, Clayton Campus Clayton 3800 Victoria Australia
contact email	anthony.purcell@monash.edu
lab head
Pouya Faridi
contact affiliation	Monash University
contact email	pouya.faridi@monash.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023044
     1. Label: PRIDE project
     2. Name: IFNγ modulates the immunopeptidome of triple negative breast cancer cells by enhancing and diversifying antigen processing and presentation.