PXD035502

PXD035502 is an original dataset announced via ProteomeXchange.

Title	Spatial proteomics of T-cell infiltrates in melanoma reveals differential regulation of TOR signaling
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2025-03-04
AnnouncementXML	Submission_2025-03-04_04:11:36.705.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannah Voß
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-21 08:19:42	ID requested
⏵ 1	2025-03-04 04:11:37	announced

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]

submitter keyword: spatial proteomics, T cell infiltrate , melanoma, immune checkpoint inhibition, LC-MS/MS

Prof. Hartmut Schlüter
contact affiliation	Section/Core Facility Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf (UKE), Martinistr. 52, 20246 Hamburg, Germany
contact email	h.schlueter@uke.de
lab head
Hannah Voß
contact affiliation	University Medical Center Hamburg Eppendorf, Institute of Clinical Chemistry and Laboratory Medicine, Group of Mass Spectrometric Proteomics
contact email	ha.voss@uke.de
dataset submitter

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/2025/03/PXD035502

PRIDE project URI

• PRIDE
  1. PXD035502
     1. Label: PRIDE project
     2. Name: Spatial proteomics of T-cell infiltrates in melanoma reveals differential regulation of TOR signaling