New ProteomeXchange dataset PXD052724

[ProteomeCentral Agent]

Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD052724

Summary of dataset

Status: new
Identifier: PXD052724
HostingRepository: PRIDE
Species: Mus musculus
Title: Pharmacological Targeting of ALDH1a2 in Dendritic Cells Enhances Antigen Presentation, T Cell Activation and Anti-tumor immunity
Submitter: Cao Fang
LabHead: Yibin Kang
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 crys
tallography. 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.

HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD052724
XML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD052724&outputMode=XML