PXD049188

PXD049188 is an original dataset announced via ProteomeXchange.

Title	PAD4 controls tumor immunity via restraining the MHC-II machinery in macrophages
Description	Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood if and how post-translational modifications (PTMs) intrinsically affect the phenotype and function of TAMs. Here, we found that peptidylarginine deiminase 4 (PAD4) manifested the highest expression among common PTM enzymes in TAMs and negatively correlated to clinical response to immune checkpoint blockade (ICB). Genetic and pharmacological inhibition of PAD4 in macrophages prevented tumor progression in tumor-bearing mouse models, accompanied by an increase in macrophage MHC-II expression and T-cell effector function. Mechanistically, PAD4 citrullinated STAT1 at arginine 121 (R121), thereby promoting the interaction between STAT1 and PIAS1; and the loss of PAD4 abolished this interaction, ablating the inhibitory role of PIAS1 in the expression of MHC-II machinery in macrophages and enhancing T-cell activation. Thus, the PAD4-STAT1-PIAS1 axis is a previously unknown intrinsic immune restriction mechanism in macrophages and may serve as a cancer immunotherapy target.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:41:25.380.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michael Pitter
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-05 12:12:29	ID requested
1	2024-05-22 11:44:38	announced
⏵ 2	2024-10-22 06:41:28	announced	2024-10-22: Updated project metadata.

10.1016/j.celrep.2024.113942;

Pitter MR, Kryczek I, Zhang H, Nagarsheth N, Xia H, Wu Z, Tian Y, Okla K, Liao P, Wang W, Zhou J, Li G, Lin H, Vatan L, Grove S, Wei S, Li Y, Zou W, PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages. Cell Rep, 43(3):113942(2024) [pubmed]

submitter keyword: T cell, macrophage, PIAS, checkpoint, MHC, immunotherapy,Tumor, PAD4, citrullination, STAT1

Weiping Zou
contact affiliation	Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
contact email	wzou@umich.edu
lab head
Michael Pitter
contact affiliation	University of Michigan
contact email	mrpitter@umich.edu
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/2024/05/PXD049188

PRIDE project URI

• PRIDE
  1. PXD049188
     1. Label: PRIDE project
     2. Name: PAD4 controls tumor immunity via restraining the MHC-II machinery in macrophages