PXD043545-1

PXD043545 is an original dataset announced via ProteomeXchange.

Title	MULTIMODAL STIMULATION SCREENS REVEAL UNIQUE AND SHARED GENES LIMITING T-CELL FITNESS
Description	T-cell dysfunction genes limit antitumor activity and may serve as therapeutic targets. It has not been systematically studied whether there are regulators that either uniquely or broadly contribute to T-cell fitness. We performed genome-scale CRISPR/Cas9 knockout screens in primary CD8 T-cells to uncover genes negatively impacting on fitness upon three modes of stimulation: (1) intense stimulation, triggering activation-induced cell death (AICD); (2) acute stimulation, triggering T-cell expansion; (3) chronic stimulation, causing dysfunction. Besides established regulators, we uncovered genes controlling T-cell fitness either specifically or commonly upon differential stimulation. Dap5 ablation, ranking highly in all three screens, increased translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T-cell clustering amplified T-cell expansion and effector functions after both acute and intense stimulation. Lastly, Ctbp1 inactivation induced functional T-cell persistence exclusively upon chronic stimulation. Our results functionally annotate fitness regulators based on their unique or shared contribution to traits limiting T-cell antitumor activity.
HostingRepository	PRIDE
AnnounceDate	2024-02-16
AnnouncementXML	Submission_2024-02-16_02:46:40.187.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Onno Bleijerveld
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-05 01:40:23	ID requested
⏵ 1	2024-02-16 02:46:40	announced
2	2024-10-22 06:30:45	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: T-cells, Dap5, exhaustion, Ctbp1, activation-induced cell death, CRISPR/Cas9 screen, Icam1, effector function, cancer immunotherapy, dysfunction

Onno B Bleijerveld
contact affiliation	NKI Proteomics Facility, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands
contact email	o.bleijerveld@nki.nl
lab head
Onno Bleijerveld
contact affiliation	The Netherlands Cancer Institute
contact email	o.bleijerveld@nki.nl
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/2024/02/PXD043545

PRIDE project URI

• PRIDE
  1. PXD043545
     1. Label: PRIDE project
     2. Name: MULTIMODAL STIMULATION SCREENS REVEAL UNIQUE AND SHARED GENES LIMITING T-CELL FITNESS