PXD043761

PXD043761 is an original dataset announced via ProteomeXchange.

Title	Tumour cells can escape antiproliferative pressure by type I interferon through immunoediting of interferon receptor expression
Description	Type I interferons (IFNs) play a central role in innate immunity against virus infection, but also in the antitumour response. In tumour biology, an important mechanism of action apart from the more indirect immune-modulatory and anti-angiogenic effects of IFNs, is their direct impact on cell proliferation. Particularly for cancers arising in the context of chronic inflammation, constant exposure of cells to IFNs may constitute a strong selective pressure during tumour evolution. Expansion of tumour subclones or -populations that developed resistance to the antiproliferative effects of IFN might constitute an important contribution to immunoediting of the tumour leading to more aggressive and metastasising disease. Experimental evidence for this development of IFN-insensitivity has been scarce and its molecular mechanism is unclear. In this study we demonstrate that prolonged (six weeks) exposure of cells to IFN-β in vitro reduces their sensitivity to its antiproliferative effects, and that this phenotype was stable for up to four weeks. Furthermore, we observed substantial differences in cellular sensitivity to growth inhibition by IFN-β in a panel of ten different liver cancer cell lines of varying malignity. IFN-resistance was most prominent in a pair of highly dedifferentiated cell lines, and least in cells from well-differentiated tumours, fostering the hypothesis of IFN-driven immunoediting in advanced cancers. In both settings, long-term IFN selection in vitro as well as in dedifferentiated tumour cell lines, we found IFNAR expression to be substantially reduced, suggesting the receptor complex, in particular IFNAR2, to be a sensitive target amenable to immunoediting. Beyond new insights into possible molecular processes in tumour evolution, these findings might prove valuable for the development of biomarkers allowing to stratify tumours for their sensitivity to IFN treatment in the context of patient tailored therapies.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:15:29.825.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcel Schilling
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-13 07:16:40	ID requested
1	2023-11-21 12:23:24	announced
⏵ 2	2024-10-22 06:15:30	announced	2024-10-22: Updated project metadata.

10.1186/S12935-023-03150-Y;

submitter keyword: interferon signalling, immunoediting, cell proliferation, tumour evolution, liver cancer

Prof. Dr. Ursula Klingmüller
contact affiliation	Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), Heidelberg, Germany
contact email	u.klingmueller@dkfz.de
lab head
Marcel Schilling
contact affiliation	Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg
contact email	m.schilling@dkfz.de
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/2023/11/PXD043761

PRIDE project URI

• PRIDE
  1. PXD043761
     1. Label: PRIDE project
     2. Name: Tumour cells can escape antiproliferative pressure by type I interferon through immunoediting of interferon receptor expression