PXD060423-1

PXD060423 is an original dataset announced via ProteomeXchange.

Title	Auranofin Fosters Regulatory T Cell Expansion and Augmented Tumor Burden in Mice
Description	Auranofin, an FDA-approved antirheumatic drug, has been reported to have anti-tumoral properties but its immunological effects and significance are not well understood. This study is the first to report auranofin-induced regulatory T cell (Treg) expansion. In a mouse model with B16F10 melanoma, auranofin treatment surprisingly resulted in increased lung tumor coverage, elevated serum IL-10 levels, and a higher frequency of FOXP3+ CD44+ CD4 T cells in the spleen compared to vehicle controls. We also noted significant differences in the relative proportions of antigen presenting cells (APCs), namely, B cells and dendritic cells (DCs). To determine if auranofin promotes Treg expansion independently of tumor-specific antigens or tumor burden, we stimulated T cell receptors ex vivo in lymph node cultures from naïve mice using anti-CD3ε/CD28 in the presence or absence of auranofin. Auranofin-treated cultures showed significantly higher Treg frequencies than controls. This phenomenon was also observed in peripheral blood mononuclear cell (PBMC) cultures from healthy donors. Results from auranofin and a specific thioredoxin reductase 1 (TRXR1) inhibitor, TRi-1, suggest that NRF2 activation through TRXR1 blockade may promote Treg expansion and immune suppression in both mice and humans. By using NCF1 deficient mice conditionally expressing functional NCF1, we found that B cell or DC specific ROS was sufficient in augmenting B16F10 tumor burden and were comparable to TRXR1 inhibitor treatment in NCF1 mutant and wild type mice. These results suggest elevated TRXR1 inhibitor induced ROS levels in APCs could trigger Treg expansion. Finally, these findings provide a rationale for the divergent anti-tumoral responses observed in auranofin-treated immunocompetent versus immunocompromised cancer models. Given the ongoing clinical trials exploring auranofin as an anti-cancer agent, this study could have clinical significance.
HostingRepository	PRIDE
AnnounceDate	2025-12-08
AnnouncementXML	Submission_2025-12-07_17:18:24.261.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Beusch
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-03 06:40:16	ID requested
⏵ 1	2025-12-07 17:18:25	announced

10.3390/antiox14111351;

Bonner MY, Vancsik T, Oliveira-Coelho A, Sabatier P, Beusch CM, Zeqiraj K, Svensson C, Zubarev RA, Arn, é, r ESJ, Holmdahl R, Anti-Tumoral Treatment with Thioredoxin Reductase 1 Inhibitor Auranofin Fosters Regulatory T Cell and B16F10 Expansion in Mice. Antioxidants (Basel), 14(11):(2025) [pubmed]

submitter keyword: Thioredoxin Reductase 1 (TRXR1), NRF2, Immune response, Treg, B16F10,Auranofin

Rikard Holmdahl
contact affiliation	Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
contact email	rikard.holmdahl@ki.se
lab head
Christian Beusch
contact affiliation	Emory University
contact email	christian.beusch@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060423
     1. Label: PRIDE project
     2. Name: Auranofin Fosters Regulatory T Cell Expansion and Augmented Tumor Burden in Mice