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PXD049188

PXD049188 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePAD4 controls tumor immunity via restraining the MHC-II machinery in macrophages
DescriptionTumor-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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:41:25.380.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMichael Pitter
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-05 12:12:29ID requested
12024-05-22 11:44:38announced
22024-10-22 06:41:28announced2024-10-22: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: T cell, macrophage, PIAS, checkpoint, MHC, immunotherapy,Tumor, PAD4, citrullination, STAT1
Contact List
Weiping Zou
contact affiliationDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
contact emailwzou@umich.edu
lab head
Michael Pitter
contact affiliationUniversity of Michigan
contact emailmrpitter@umich.edu
dataset submitter
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Dataset FTP location
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