PXD029507

PXD029507 is an original dataset announced via ProteomeXchange.

Title	Enhanced antigen cross-presentation in human colorectal cancer-associated fibroblasts through upregulation of the lysosomal protease Cathepsin S
Description	Cross-presentation of exogenous antigens in HLA-class I molecules by professional antigen presenting cells (APCs) is crucial for CD8+ T cell function. Recent murine studies show that several non-professional APCs, including cancer-associated fibroblasts (CAFs) also possess this capacity. It is currently unknown whether human CAFs are able to cross-present exogenous antigen, which molecular pathways are involved in this process and how this ultimately affects tumor-specific CD8+ T cell function. Here we show that human colorectal cancer (CRC)-derived CAFs display an enhanced capacity to cross-present neoantigen-derived synthetic long peptides (SLPs) when compared to normal colonic fibroblasts. Importantly, cross-presentation of antigens required the lysosomal protease Cathepsin S. Cathepsin S expression by CAFs was detected in situ in human CRC tissue, was upregulated in ex vivo cultured CRC-derived CAFs and showed increased expression in normal fibroblasts after exposure to CRC-conditioned medium. Cognate interaction between CD8+ T cells and cross-presenting CAFs suppressed T cell function, reflected by decreased cytotoxicity, reduced activation (CD25, CD137) and increased exhaustion (TIM3) marker expression. Our data indicate that CAFs may directly suppress tumor-specific T cell function in an antigen-dependent fashion in human CRC.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:35:09.397.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	G Janssen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-02 03:55:50	ID requested
1	2022-03-03 12:54:41	announced
⏵ 2	2024-10-22 05:35:09	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Tumor immunology, Non-professional antigen presentation,Parallel reaction monitoring, Stromal immunobiology

P.A. van Veelen
contact affiliation	Head Proteomics Group, Center for Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
contact email	p.a.van_veelen@lumc.nl
lab head
G Janssen
contact affiliation	Leiden University Medical Center
contact email	g.m.c.janssen@lumc.nl
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/2022/03/PXD029507

PRIDE project URI

• PRIDE
  1. PXD029507
     1. Label: PRIDE project
     2. Name: Enhanced antigen cross-presentation in human colorectal cancer-associated fibroblasts through upregulation of the lysosomal protease Cathepsin S