PXD034623

PXD034623 is an original dataset announced via ProteomeXchange.

Title	Galectin-1 upregulates IDO1 and PD-L1 and induces a tolerogenic tumor-associated M2 macrophage phenotype
Description	Galectins are a group of carbohydrate binding proteins with immunomodulatory functions. While the effects of galectins on the T cell compartment are well described, the interactions between galectins and antigen-presenting cells (APCs) remain elusive. Here we find increased expression of galectin-1(gal-1) in the stroma of a large selection of cancers, and investigating the effect of gal-1 on stroma localized antigen presenting cells, including monocyte derived dedritic cells and M1 and M2 macrophages (M1s and M2s, respectively). Using an in depth and dynamic proteomic and phosphoproteomic analysis of the effect of gal-1 on M2s we show that gal-1 induces global changes in the proteomic and signaling landscape of M2s, consistent with induction of a tolerogenic macrophage phenotype. Specifically, gal-1 induces expression of key immunomodulatory and tumor-associated proteins, including the key immune checkpoint protein, programmed cell death 1 ligand 1 (PD-L1/CD274) and the immunomodulator, indoleamine 2,3-dioxygenase-1 (IDO1). Gal-1 induced IDO1 and its active metabolite kynurenine in a dose dependent manner, an effect that was prevented by JAK/STAT inhibition. Analyzing gal-1 expression in human tumors we find that gal-1 is upregulated across multiple tumors, and in a 3D organotypic model system equipped with genetically engineered tumorigenic epithelial cells, we find that the tumor associated gal-1 is derived from both from epithelial and stromal cells. Our results highlight the potential of targeting gal-1 in immunotherapeutic treatment of human cancers.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_06:51:27.072.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zilu Ye
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-17 07:54:22	ID requested
1	2023-08-14 04:48:26	announced
⏵ 2	2023-11-14 06:51:27	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Galectin, macrophage, IDO1, PD-L1/CD274, LC-MS/MS

Jesper Velgaard Olsen
contact affiliation	Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark
contact email	jesper.olsen@cpr.ku.dk
lab head
Zilu Ye
contact affiliation	University of Copenhagen
contact email	yezlandss@gmail.com
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/2023/08/PXD034623

PRIDE project URI

• PRIDE
  1. PXD034623
     1. Label: PRIDE project
     2. Name: Galectin-1 upregulates IDO1 and PD-L1 and induces a tolerogenic tumor-associated M2 macrophage phenotype