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PXD028037

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
PRIDE project URI
Repository Record List
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