PXD051467

PXD051467 is an original dataset announced via ProteomeXchange.

Title	Tailoring vascular-immune homeostasis via magnesium-DNA complex-armed immunogenic vesicles for pancreatic cancer immunotherapy
Description	Leveraging the cGAS-STING DNA sensing pathway in dendritic cells (DCs) for anti-pancreatic tumor immunity is challenging due to activation constraints, particularly in the context of pancreatic cancer's immunotherapeutic resistance. Recent research indicates that magnesium (Mn2+) enhances cGAS sensitivity to DNA, although the precise mechanism remains unclear. In this study, we demonstrate that the addition of Mn2+ increases the affinity of tumor cell-DNA binding to cGAS. Utilizing a Raft-Ultra method, we engineered immunogenic extracellular vesicles (EVs) derived from tumor cell lysate-pulsed DCs, loaded with Mn-DNA complexes (EVDC@Mn-DNA). These EVs efficiently deliver DNA to DCs, activating the cGAS-STING pathway both in vitro and in vivo. Animal experiments reveal that administering EVDC@Mn-DNA enhances vascular function, as evidenced by increased blood flow/perfusion, improved anti-PD-L1 delivery, reduced hypoxia, and elevated endothelial expression of the T cell adhesion molecule ICAM1. Furthermore, this treatment promotes the intratumor population of activated DCs and T cells and increases the sizes of tertiary lymphoid structures, thereby restraining orthotopic pancreatic tumor growth. Overall, our EVDC@Mn-DNA strategy activates intratumor DCs, restoring vascular-immune cell homeostasis and stimulating anti-tumor immunity in pancreatic cancer.
HostingRepository	iProX
AnnounceDate	2024-04-15
AnnouncementXML	Submission_2024-04-15_20:27:05.200.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xue Jiang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606; scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-15 20:26:31	ID requested
⏵ 1	2024-04-15 20:27:05	announced

Dataset with its publication pending

submitter keyword: Tumor Microenvironment, Dendritic cell, STING, Immunotherapy, Pancreatic cancer

Pingpui Wong
contact affiliation	Sun Yat-sen Memorial Hospital, Sun Yat-sen University
contact email	huangbp3@mail.sysu.edu.cn
lab head
Xue Jiang
contact affiliation	Sun Yat-sen Memorial Hospital, Sun Yat-sen University
contact email	915143522@qq.com
dataset submitter

iProX dataset URI