<<< Full experiment listing

PXD028037-1

PXD028037 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA lysosome-targeted DNA nanodevice selectively targets macrophages to attenuate tumors
DescriptionActivating CD8+ T cells by antigen cross-presentation is remarkably effective at eliminating tumors. Although this function is traditionally attributed to dendritic cells, tumor-associated macrophages (TAMs) can also cross-present antigens. TAMs are the most abundant tumor-infiltrating leukocyte. Yet, TAMs have not been leveraged to activate CD8+ T cells because mechanisms that modulate their ability to cross-present antigens are incompletely understood. Here we show that TAMs harbor hyperactive cysteine protease activity in their lysosomes which impedes antigen cross-presentation, thereby preventing CD8+ T cell activation. We developed a DNA nanodevice (E64-DNA) targeted to lysosomes of TAMs in mice. E64-DNA inhibits the population of cysteine proteases present specifically inside lysosomes of TAMs, improves their ability to cross-present antigens, and attenuates tumor growth via CD8+ T cells. When combined with cyclophosphamide, E64-DNA showed sustained tumor regression in a triple-negative-breast-cancer model. Our studies demonstrate that DNA nanodevices can be targeted with organelle-level precision to reprogram macrophages and achieve immunomodulation in vivo.
HostingRepositoryPRIDE
AnnounceDate2021-10-14
AnnouncementXMLSubmission_2021-10-13_23:17:16.678.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTomas Vaisar
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-08-19 21:41:17ID requested
12021-10-13 23:17:17announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Macrophages, lysosomes, cysteine proteases, antigen cross-presentation, cancer, LC-MSMS
Contact List
Lev Becker
contact affiliationBen May Department of Cancer Research, University of Chicago
contact emaillevb@chicago.edu
lab head
Tomas Vaisar
contact affiliationUniversity of Washington
contact emailtvaisar@uw.edu
dataset submitter
Full Dataset Link List
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/2021/10/PXD028037
PRIDE project URI
Repository Record List
[ + ]