PXD055157

PXD055157 is an original dataset announced via ProteomeXchange.

Title	MGAT1-Mediated Glycosylation Orchestrates Immune Checkpoints and Antitumor Immunity
Description	Despite the widespread application of immunotherapy, treating immune-cold tumors remains a significant challenge in cancer therapy. Using multiomic spatial analyses and experimental validation, we have identified MGAT1, a glycosyltransferase, as a pivotal factor governing tumor immune response. Overexpression of MGAT1 leads to immune evasion due to aberrant elevation of CD73 membrane translocation, which suppresses CD8+ T cell function, especially in immune-cold triple-negative breast cancer (TNBC). Mechanistically, addition of N-acetylglucosamine to CD73 by MGAT1 enables the CD73 dimerization necessary for CD73 loading onto VAMP3, ensuring membrane fusion. We further show that THBS1 is an upstream etiological factor orchestrating the MGAT1-CD73-VAMP3-adenosine axis in suppressing CD8+ T cell antitumor activity. Spatial transcriptomic profiling reveals spatially resolved features of interacting malignant and immune cells pertaining to expression levels of MGAT1 and CD73. In preclinical models of TNBC, W-GTF01, a newly developed inhibitor, specifically blocked the MGAT1-catalyzed CD73 glycosylation, sensitizing refractory tumors to anti-PD-L1 therapy via restoring capacity to elicit a CD8+ IFNγ-producing T cell response. Collectively, our findings uncover a strategy for targeting the immunosuppressive molecule CD73 by inhibiting MGAT1.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_01:32:22.262.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Junlong CHI
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-23 16:54:33	ID requested
⏵ 1	2025-05-07 01:32:23	announced

Chi JJ, Xie P, Cheng MH, Zhu Y, Cui X, Watson J, Zeng L, Uddin A, Nguyen H, Li L, Moremen K, Reedy A, Wyatt M, Marcus A, Dai M, Paulos CM, Cristofanilli M, Gradishar WJ, Zhao S, Kalinsky K, Hung MC, Bahar I, Zhang B, Wan Y, MGAT1-Guided complex N-Glycans on CD73 regulate immune evasion in triple-negative breast cancer. Nat Commun, 16(1):3552(2025) [pubmed]

10.1038/s41467-025-58524-9;

submitter keyword: MGAT1

glycosylation

CD73

tumor immunogenicity

drug design and therapeutics

Yong Wan
contact affiliation	Department of Pharmacology and Chemical Biology, Emory University, USA
contact email	yong.wan@emory.edu
lab head
Junlong CHI
contact affiliation	Emory University
contact email	jchi22@emory.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/2025/05/PXD055157

PRIDE project URI

• PRIDE
  1. PXD055157
     1. Label: PRIDE project
     2. Name: MGAT1-Mediated Glycosylation Orchestrates Immune Checkpoints and Antitumor Immunity