PXD069576

PXD069576 is an original dataset announced via ProteomeXchange.

Title	Tumor-derived CDC37 inhibits antigen cross-presentation in dendritic cells and impairs anti-tumor immunity in breast cancer
Description	Tumor mutational burden (TMB), usually representing high immunogenicity, could not always predict treatment response of immune checkpoint blockade (ICB). Here, we showed that defective antigen cross-presentation in type 1 conventional dendritic cells (cDC1) was responsible for lacking tumor-specific cytotoxic T lymphocytes (CTLs) in triple-negative breast cancer (TNBC) patients. Mechanistically, tumor cytosolic CDC37, shuttled via extracellular vesicles (EVs) into the endosomes of intratumor DCs, inhibited antigen cross-presentation by locking antigen binding to HSP90 and precluding their translocation from endosomes to cytoplasm. CDC37 knockdown in tumor cells or inhibiting CDC37/HSP90 interaction in DCs efficiently promoted antigen translocation and enhanced their cross-presentation, which improved ICB therapeutic responses. Clinically, high tumor CDC37 expression was associated with low infiltration of antigen-specific CTLs and poor ICB efficacy in TNBC patients. Therefore, tumor EV-shuttled CDC37 locks antigen/chaperone interaction and impairs antigen cross-presentation in DCs. Moreover, targeting CDC37 is promising to enhance anti-tumor immunity and reverse ICB resistance.
HostingRepository	iProX
AnnounceDate	2025-10-17
AnnouncementXML	Submission_2025-10-17_00:28:46.277.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yunyi Zhang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-17 00:28:14	ID requested
⏵ 1	2025-10-17 00:28:46	announced

Dataset with its publication pending

submitter keyword: antigen cross-presentation, type 1 conventional dendritic cell, immune checkpoint blockades, extracellular vesicles, CDC37

Di Huang
contact affiliation	Sun Yat-sen Memorial Hospital,Sun Yat-sen University
contact email	huangd63@mail.sysu.edu.cn
lab head
Yunyi Zhang
contact affiliation	Sun Yat-sen Memorial Hospital,Sun Yat-sen University
contact email	zhangyy223@mail2.sysu.edu.cn
dataset submitter

iProX dataset URI