PXD044028

PXD044028 is an original dataset announced via ProteomeXchange.

Title	PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation
Description	The cell surface receptor programmed death 1 (PD1) is a major target for antibody-based cancer immunotherapies. An improved understanding of intracellular pathways targeted by PD1 is needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering reduces the phosphorylation and physical association with PKC theta of a variety of cytoskeletal proteins. TCR-induced phosphorylation of Vimentin, a cytoskeleton protein identified as a PKC theta target and binding partner in our study, was found to be long-lasting and durably inhibited by PD1 triggering, and Vimentin phosphorylation inversely correlated with PDL1 levels in intratumoral T cells in human lung carcinoma. Thus, PKCθ and its substrate Vimentin represent important targets of PD1-mediated T cell inhibition and low levels of Vimentin phosphorylation could be considered as a biomarker indicating PD1 pathway engagement.
HostingRepository	PRIDE
AnnounceDate	2024-04-19
AnnouncementXML	Submission_2024-04-19_00:51:07.051.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Manfredo Quadroni
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion; Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-24 04:20:50	ID requested
⏵ 1	2024-04-19 00:51:07	announced

10.1182/BLOODADVANCES.2023011901;

submitter keyword: T-cell activation , PD-1 , phosphoproteomics, immune synapse , cancer immunotherapy

Margot Thome
contact affiliation	Department of Immunobiology University of Lausanne Chemin des Boveresses 155 CH-1066 Epalinges, Switzerland
contact email	Margot.ThomeMiazza@unil.ch
lab head
Manfredo Quadroni
contact affiliation	University of Lausanne
contact email	manfredo.quadroni@unil.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044028
     1. Label: PRIDE project
     2. Name: PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation