PXD058576

PXD058576 is an original dataset announced via ProteomeXchange.

Title	CSF1R-CAR T cells induce CSF1R signaling and promote target cell growth
Description	Chimeric antigen receptor (CAR) T cells have revolutionized the landscape of cancer therapy, demonstrating unprecedented success in treating relapsed or refractory blood cancers. Previous studies of the mechanisms underlying the interactions and responses of CAR T cells and their targets have focused on the activation of CAR T cells and attempted to optimize CAR design to increase efficacy, while ignoring tumors and their responses to CAR ligation. We evaluated the signaling of a second-generation, ligand-based CAR built from the colony-stimulating factor 1 (CSF1) ligand to target the CSF1 receptor (CSF1R) on CSF1R-expressing target cells, and compared it to a conventional single-chain variable fragment (scFv)–based CAR against the B-cell antigen CD19 using stable isotope labeling by amino acids in cell culture (SILAC) co-culture with phosphotyrosine (pY) enrichment and liquid chromatography–tandem mass spectrometry (LC–MS/MS).. We showed that ligation of CSF1R-expressing THP-1 cells with CSF1R-CAR T cells stimulated CSF1R-like signaling in the THP-1 cells, whereas no target cell signaling response was observed after the ligation of CD19-CAR T cells with target Raji cells. In experiments with small-molecule inhibitors of the tyrosine kinase Lck, actin polymerization, and CSF1R, we found that CAR-induced CSF1R signaling in THP-1 cells depended exclusively on the kinase activity of CSF1R with no participation from T cell activation. Consistently, CSF1R-CAR T cells promoted THP-1 cell growth at low effector-to-target (E:T) ratios but prevented THP-1 cell growth at high E:T ratios. Our data provide evidence for an unintended consequence of CARs: CAR-induced signaling in cancer cells. These data may have broad implications for the choice of CAR antigen for optimal clinical efficacy.
HostingRepository	PRIDE
AnnounceDate	2025-11-21
AnnouncementXML	Submission_2025-11-21_08:50:30.997.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Arthur Salomon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-04 09:03:56	ID requested
⏵ 1	2025-11-21 08:50:31	announced

Callahan A, Zhang X, Wang A, Mojumdar A, Zeng L, Su X, Salomon AR, CSF1R-CAR T cells induce CSF1R signaling and can promote target cell proliferation. Sci Signal, 18(912):eadv4112(2025) [pubmed]

10.1126/scisignal.adv4112;

submitter keyword: None

Arthur Robert
contact affiliation	Brown University MCB Department
contact email	drsalomon@gmail.com
lab head
Arthur Salomon
contact affiliation	Brown University
contact email	art@drsalomon.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/2025/11/PXD058576

PRIDE project URI

• PRIDE
  1. PXD058576
     1. Label: PRIDE project
     2. Name: CSF1R-CAR T cells induce CSF1R signaling and promote target cell growth