PXD049188 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD049188
- Label: PRIDE project
- Name: PAD4 controls tumor immunity via restraining the MHC-II machinery in macrophages