PXD034897

PXD034897 is an original dataset announced via ProteomeXchange.

Title	Concomitant deletion of Shp-1 and Shp-2 in T cells fails to improve anticancer responses
Description	Anticancer T cells acquire a dysfunctional state characterized by poor effector function and expression of inhibitory receptors, such as programmed cell death protein 1 (PD-1). Blockade of PD-1 signalling leads to T cell reinvigoration and is increasingly applied as an effective anticancer treatment. Recent work challenged the commonly held view that the phosphatase Src homology 2 (SH2) domain–containing phosphatase (SHP)-2 is essential for the molecular cascade downstream PD-1, suggesting functional redundancy with the homologous phosphatase SHP-1. Therefore, we investigated the effect of concomitant SHP-1 and 2 deletion in T cells on their ability to mount antitumour immune responses. In vivo data shows that neither sustained or acute SHP-1/2 deletion improves T cell mediated tumour control. The loss of SHP-1/2 also impairs the therapeutic effects of anti-PD1 treatment. In vitro results show that SHP-1/2-deleted CD8+ T cells exhibit impaired expansion due to a survival defect and proteomics analysis reveals substantial alterations in their proteome, including in apoptosis-related pathways. This data indicates that concomitant ablation of SHP-1/2 in polyclonal T cells fails to improve their anticancer properties, implying that caution shall be taken when considering their inhibition for immunotherapeutic approaches.
HostingRepository	PRIDE
AnnounceDate	2022-09-29
AnnouncementXML	Submission_2022-09-29_07:00:14.558.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Spinelli
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-26 07:30:07	ID requested
⏵ 1	2022-09-29 07:00:14	announced

Dataset with its publication pending

submitter keyword: Shp-2

Shp-1

Ptpn11

Ptpn6

T cell exhaustion

cancer immunotherapy

inhibitory receptors

PD-1 checkpoint therapy

Doreen Cantrell
contact affiliation	Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee
contact email	d.a.cantrell@dundee.ac.uk
lab head
Laura Spinelli
contact affiliation	Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, DD1 5EH Dundee, U.K.
contact email	l.z.spinelli@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034897
     1. Label: PRIDE project
     2. Name: Concomitant deletion of Shp-1 and Shp-2 in T cells fails to improve anticancer responses