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PXD035502

PXD035502 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSpatial proteomics of T-cell infiltrates in melanoma reveals differential regulation of TOR signaling
DescriptionThe tumor microenvironment determines the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking. To better understand and assess targetable promising biological processes that specifically determine the tumor T cell infiltrate (TiLs), we mapped the spatial distribution of proteins in TiL-enriched vs. low compartments in melanoma by combining microscopy, MALDI-MSI-based imaging and liquid chromatography-mass spectrometry (LC-MS/MS), and computational data mining. Using a spatial proteome algorithm and gene ontology-based enrichment analysis, we identified >145 proteins that were differentially expressed in CD8high tumor compartments including negative regulators of the mTOR signaling such as sirtuin 1 (SIRT1). Multiplexed immunohistochemistry confirmed that SIRT1 protein was higher expressed in CD8high compared to CD8low compartments and present in both CD8+ TiLs and CD8- cell types. Complementary analysis of bulk and single cell RNAseq data suggested expression of SIRT1 by different lymphocyte subpopulations (CD8+ T, CD4+ T and B cells) in close proximity to melanoma cells. We demonstrated in a syngeneic ICI-sensitive mouse melanoma model that the SIRT1 inhibitor EX-527 reduces the anti-tumor effect of α-PD1 ICI accompanied by decreased CD4+ and CD8+ TiLs in the tumor margin. In silico analysis of large transcriptional data cohorts showed that SIRT1 is positively associated with the proinflammatory T-cell chemokines CXCL-9, -10, and IFN-γ, and prolonged overall survival of melanoma patients. Our study concludes that spatial proteomics by MALDI-MSI is a promising technology to characterize the functional tumor microenvironment providing an important mechanistic layer of biologic information for the identification of protein candidates with important prognostic and therapeutic implications.
HostingRepositoryPRIDE
AnnounceDate2025-03-04
AnnouncementXMLSubmission_2025-03-04_04:11:36.705.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHannah Voß
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-07-21 08:19:42ID requested
12025-03-04 04:11:37announced
Publication List
10.1093/bjd/ljae433;
Placke JM, Bottek J, V, á, raljai R, Shannan B, Scharfenberg S, Krisp C, Spangenberg P, Soun C, Siemes D, Borgards L, Hoffmann F, Zhao F, Paschen A, Schlueter H, von Eggeling F, Helfrich I, Rambow F, Ugurel S, Tasdogan A, Schadendorf D, Engel DR, Roesch A, Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma. Br J Dermatol, 192(3):481-491(2025) [pubmed]
Keyword List
submitter keyword: spatial proteomics, T cell infiltrate , melanoma, immune checkpoint inhibition, LC-MS/MS
Contact List
Prof. Hartmut Schlüter
contact affiliationSection/Core Facility Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf (UKE), Martinistr. 52, 20246 Hamburg, Germany
contact emailh.schlueter@uke.de
lab head
Hannah Voß
contact affiliationUniversity Medical Center Hamburg Eppendorf, Institute of Clinical Chemistry and Laboratory Medicine, Group of Mass Spectrometric Proteomics
contact emailha.voss@uke.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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