PXD058770

PXD058770 is an original dataset announced via ProteomeXchange.

Title	Deletion of Egfr in myeloid cells counteracts an immuno-suppressive tumor microenvironment in CRC
Description	Despite advances in metastatic colorectal cancer (mCRC) treatment, it remains the second-leading cause of cancer-related deaths, with limited therapeutic options. EGFR inhibition is a first-line treatment for mCRC without KRAS mutations, but resistance persists in some patients. Preclinical murine CRC models have shown that EGFR deletion in myeloid cells results in smaller tumors, while the presence of EGFR-positive myeloid cells correlate with poor survival in mCRC patients. However, the role of these cells in tumor progression remains unclear. In this study, we used preclinical mouse models, scRNA-seq, proteomics, and mCRC patient data to investigate the impact of EGFR expression in myeloid cells on the tumor microenvironment (TME) and explore its therapeutic potential. We demonstrate that EGFR deletion in myeloid cells of tumor-bearing CRC mice reduces tumor growth, while EGFR deletion in tumor cells alone has no therapeutic effect. EGFR disruption also decreases F4/80hi macrophages, particularly Spp1+ and C1qc+ subsets, and reduces inflammatory signaling like TGFβ, IFNγ, JAK/STAT in myeloid cells. This, in turn, affects their interaction with T cells, promoting a shift towards a less immunosuppressive TME. Additionally, we identify reduced immune checkpoint expression and thrombospondin-1 (Thbs1) as a myeloid-derived ligand interacting with T-cells. Validation in human CRC shows that high expression of EGFR and THBS1 correlates with poorer prognosis. These findings highlight EGFR signaling in myeloid cells as a key modulator of the TME and suggest targeting EGFR in specific myeloid subsets could improve CRC treatment strategies.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-08_01:54:24.287.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcel Schilling
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-11 04:42:57	ID requested
⏵ 1	2026-06-08 01:54:25	announced

10.1038/s41418-026-01774-x;

Fari O, Neuhofer A, Holcmann M, Chontorotzea T, Barozzi I, Mohr T, Blauensteiner B, Krau, ß D, Xiao YT, Lang M, Frey DL, Helm B, Klingm, ü, ller U, Farlik M, Sibilia M, deletion in myeloid cells reprograms the immunosuppressive landscape of colorectal cancer. Cell Death Differ, ():(2026) [pubmed]

submitter keyword: Mouse, scRNA-seq, metastatic colorectal cancer (mCRC), EGFR signaling

Prof. Ursula Klingmüller
contact affiliation	German Cancer Research Center (DKFZ),Division Systems Biology of Signal Transduction, INF 280, 69120 Heidelberg
contact email	u.klingmueller@dkfz-heidelberg.de
lab head
Marcel Schilling
contact affiliation	Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg
contact email	m.schilling@dkfz.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/2026/06/PXD058770

PRIDE project URI

• PRIDE
  1. PXD058770
     1. Label: PRIDE project
     2. Name: Deletion of Egfr in myeloid cells counteracts an immuno-suppressive tumor microenvironment in CRC