ArticleBritish journal of cancer2025
IL-10RA governor the expression of IDO in the instruction of lymphocyte immunity.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Rearming mesenchymal stem cells with engineering strategies to combat cancer.Frontiers in immunology · 2026Review
- Extracellular vesicles derived from TNF-α-preconditioned mesenchymal stem cells mitigate inflammatory retinal injury.Extracellular vesicles and circulating nucleic acids · 2026Article
- Transcriptomic analysis reveals that BVDV alters immune and metabolic responses toFrontiers in veterinary science · 2026Article
- Inflammation-related proteomics of extracellular vesicles as novel biomarkers for systemic lupus erythematosus revealed by proximity extension assay.Arthritis research & therapy · 2025Article
- Applications and challenges of patient-derived organoids in hepatobiliary and pancreatic cancers.World journal of gastroenterology · 2025Review
- AIF1L as a Ferroptosis-Linked Biomarker in Microsatellite States-Driven Colorectal Cancer: Functional and Diagnostic Insights From Multiomics Analysis.Human mutation · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
backgroundIndoleamine 2,3-dioxygenase (IDO) impairs anti-pathogen and anti-tumour immunity. Mesenchymal stem cells (MSCs) modulate immunity via IDO but also suppress IFN-γ. While MSC IDO induction by IFN-γ is established, other drivers in this immunosuppressive setting remain unknown.
methodsHuman bone marrow mesenchymal stem cells (MSCs) with IDO or IL-10RA knockdown were co-cultured with healthy donor T cells to assess immunosuppression. PDAC organoid anticancer activity was also tested in these co-cultures.
resultsCo-culturing MSCs with T cells in an IL-10RA-enriched environment enhances IDO expression, resulting in T cell suppression. Moreover, IL-10RA-positive MSCs collected from co-cultures with IL-10 supplementation show increased IDO expression. Conversely, MSCs with IL-10RA knockdown exhibit a significant reduction in IDO RNA and protein expression, as well as STAT3 phosphorylation status, which is a known upstream signalling pathway in IDO gene regulation, in T cell co-cultures. Down-regulation of IL-10RA also inhibits IDO activity in MSCs, resulting in reduced T cell suppression, and enabling the co-cultured T cells to kill PDAC organoids.
conclusionOur research reveals IL-10RA as a pharmacological target in stromal cells for enhancing T cell-mediated PDAC eradication by downregulating IDO via blocked IL-10/IL-10RA signalling in MSCs. This advances IL-10RA interference in the tumour microenvironment (TME) to restore T cell cytotoxicity against cancers.
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