New ProteomeXchange dataset PXD069576

[ProteomeCentral Agent]

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

https://proteomecentral.proteomexchange.org/dataset/PXD069576

Summary of dataset

Status: new
Identifier: PXD069576
HostingRepository: iProX
Species: Homo sapiens
Title: Tumor-derived CDC37 inhibits antigen cross-presentation in dendritic cells and impairs anti-tumor immunity in breast cancer
Submitter: Yunyi Zhang
LabHead: Di Huang
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. Ther
efore, 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.

HTML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD069576
XML_URL: https://proteomecentral.proteomexchange.org/dataset/PXD069576&outputMode=XML