PXD052724

PXD052724 is an original dataset announced via ProteomeXchange.

Title	Pharmacological Targeting of ALDH1a2 in Dendritic Cells Enhances Antigen Presentation, T Cell Activation and Anti-tumor immunity
Description	Dendritic cell (DC) vaccines have been proposed as cancer immunotherapies due to their role as crucial antigen-presenting cells that regulate T cell functions. Despite considerable efforts to optimize ex vivo priming of DCs, DC vaccines have rarely been successful, suggesting the presence of unknown inhibitory factors. Here, we examined DC differentiation dynamics and discovered that ALDH1a2-produced retinoic acid (RA) acts as a bottleneck factor, initiating negative feedback to inhibit DC maturation. Removing this inhibition through either genetic knockout or pharmacological blockade using KyA33, an ALDH1a2 inhibitor we developed, significantly enhances DC maturation, phagocytosis, antigen presentation, and T cell activation, in part by downregulating glucose metabolism. KyA33 demonstrates favorable drug-like properties, including low toxicity, high membrane permeability, and low cell efflux rate. Its non-covalent binding to ALDH1A2 was also validated through X-ray crystallography. Importantly, application of KyA33 generates more robust DCs vaccines, promoting anti-tumor immunity through enhancing antigen-specific T cell responses. Our investigation highlights the intricate interplay between retinoid signaling, dendritic cell maturation, and immune metabolism, offering promising avenues for enhancing cancer immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2025-12-19
AnnouncementXML	Submission_2025-12-18_22:47:57.640.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Cao Fang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-30 10:00:44	ID requested
⏵ 1	2025-12-18 22:47:58	announced

10.1038/S41590-025-02376-4;

submitter keyword: T cell activation,Dendritic cells, ALDH inhibitors, DC vaccines

Yibin Kang
contact affiliation	Department of Molecular Biology, Princeton University
contact email	ykang@princeton.edu
lab head
Cao Fang
contact affiliation	Princeton University
contact email	caof@princeton.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/2025/12/PXD052724

PRIDE project URI

• PRIDE
  1. PXD052724
     1. Label: PRIDE project
     2. Name: Pharmacological Targeting of ALDH1a2 in Dendritic Cells Enhances Antigen Presentation, T Cell Activation and Anti-tumor immunity