PXD040436-2

PXD040436 is an original dataset announced via ProteomeXchange.

Title	TIMP1 mediates astrocyte-dependent local immunosuppression in brain metastasis acting on infiltrating CD8+ T cells.
Description	Immunotherapies against brain metastases have shown clinical benefits mainly when applied to locally asymptomatic patients. It is currently unclear why responses to this therapy drop in symptomatic brain metastases, since the use of corticoids is not consistently involved. We report here that a subpopulation within STAT3+ brain metastasis-associated astrocytes is responsible to block the anti-tumor activity of infiltrating CD8+ T cells. The underlying molecular crosstalk involving astrocyte-secreted TIMP1 signaling on CD63+ CD8+ T cells proves a strong immunomodulatory role of astrocytes in the context of brain metastases. By using genetic and pharmacologic approaches applied not only to mouse models, but also to alive human brain metastases we conclude that a combined immunotherapy blocking this local immunosuppressive hub could benefit patients with symptomatic brain metastases. Furthermore, the detection of TIMP1 in the CSF provides a biomarker to select patients for this therapeutic approach. Our findings uncover the importance of dissecting the heterogeneity within the microenvironment at the functional level and the emerging cellular networks to improve the efficacy of organ-specific therapies in metastasis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:56:43.311.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fernando Garcia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-27 06:00:59	ID requested
1	2024-08-27 04:13:52	announced
⏵ 2	2024-10-22 06:56:43	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: microenvironment,Brain metastasis, immunotherapy

Fernando Garcia
contact affiliation	Fernando Garcia Martinez Ph.D. Proteomics & MS Specialist Proteomics Unit, Spanish National Cancer Research Centre (CNIO) Melchor Fernández Almagro 3. E28029 MADRID, SPAIN. Phone +34 912246900 ext 3112
contact email	fgarcia@cnio.es
lab head
Fernando Garcia
contact affiliation	Fernando García Martínez, Ph.D. Proteomics Unit, Spanish National cancer Research Center, CNIO, MADRID, SPAIN
contact email	fgarcia@cnio.es
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/2024/08/PXD040436

PRIDE project URI

• PRIDE
  1. PXD040436
     1. Label: PRIDE project
     2. Name: TIMP1 mediates astrocyte-dependent local immunosuppression in brain metastasis acting on infiltrating CD8+ T cells.