PXD039463

PXD039463 is an original dataset announced via ProteomeXchange.

Title	Breast cancer stem cell-derived tumors escape from γδ T cell immunosurveillance in vivo by modulating γδ T cell ligands
Description	Triple negative breast cancer (TNBC) lacks targeted therapy options. TNBC is enriched in breast cancer stem cells (BCSCs), which play a key role in metastasis, chemoresistance, relapse and mortality. γδ T cells hold great potential in immunotherapy against cancer, and might be an alternative to target TNBC. γδ T cells are commonly observed to infiltrate solid tumors and have an extensive repertoire of tumor sensing, recognizing stress-induced molecules and phosphoantigens (pAgs) on transformed cells. We show that patient derived triple negative BCSCs are efficiently recognized and killed by ex vivo expanded γδ T cells from healthy donors. Orthotopically xenografted BCSCs, however, were refractory to γδ T cell immunotherapy. Mechanistically, we unraveled concerted differentiation and immune escape: xenografted BCSCs lost stemness, expression of γδ T cell ligands, adhesion molecules and pAgs, thereby evading immune recognition by γδ T cells. Indeed, neither pro-migratory engineered γδ T cells, nor anti-PD 1 checkpoint blockade significantly prolonged overall survival of tumor-bearing mice. BCSC immune escape was independent of the immune pressure exerted by the γδ T cells, and could be pharmacologically reverted by Zoledronate or IFN-α treatment. These results pave the way for novel combinatorial immunotherapies for TNBC.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:03:32.297.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD039463
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Renata Soares
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-16 04:02:19	ID requested
1	2023-07-20 11:42:10	announced
⏵ 2	2023-11-14 09:03:37	announced	2023-11-14: Updated project metadata.

10.6019/PXD039463;

Raute K, Strietz J, Parigiani MA, Andrieux G, Thomas OS, Kistner KM, Zintchenko M, Aichele P, Hofmann M, Zhou H, Weber W, Boerries M, Swamy M, Maurer J, Minguet S, T-cell Ligands. Cancer Immunol Res, 11(6):810-829(2023) [pubmed]

submitter keyword: breast cancer stem cells, proteomics, TMT, immune-escape, LC-MS, quantitation, immunotherapy, γδ T cells, phosphoantigens,Triple negative breast cancer

Mahima Swamy
contact affiliation	Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dundee, UK
contact email	m.swamy@dundee.ac.uk
lab head
Renata Soares
contact affiliation	MRC-PPU, University of Dundee
contact email	r.filipesoares@dundee.ac.uk
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/2023/07/PXD039463

PRIDE project URI

• PRIDE
  1. PXD039463
     1. Label: PRIDE project
     2. Name: Breast cancer stem cell-derived tumors escape from γδ T cell immunosurveillance in vivo by modulating γδ T cell ligands