ArticleLiver international : official journal of the International Association for the Study of the Liver2023
DKK1 drives immune suppressive phenotypes in intrahepatic cholangiocarcinoma and can be targeted with anti-DKK1 therapeutic DKN-01.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Factors affecting the role of canonical Wnt inhibitor Dickkopf-1 in cancer progression.Frontiers in oncology · 2023Pooled it
- Advances in Immunotherapy for Intrahepatic Cholangiocarcinoma.International journal of molecular sciences · 2026Review
- DKK1 in Cancer: A Bench-to-Bedside Review of Molecular Mechanisms and Clinical Applications.Cancers · 2026Review
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- Modulation of β-Catenin promotes WNT expression in macrophages and mitigates intestinal injury.Cell communication and signaling : CCS · 2025Article
- Stroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer.Nature communications · 2025Article
- The Immune-Genomics of Cholangiocarcinoma: A Biological Footprint to Develop Novel Immunotherapies.Cancers · 2025Review
- CLDN18.2: a potential nanotherapeutic target for cholangiocarcinoma.Frontiers in pharmacology · 2025Review
- Characterization of cell states in biliary tract cancers identifies mechanisms of therapeutic resistance in a phase II trial of DKN-01/nivolumab.medRxiv : the preprint server for health sciences · 2024Article
- Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities.PLoS neglected tropical diseases · 2024Article
- Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression.Frontiers in immunology · 2024Review
- Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer.Cancer management and research · 2024Review
- [Exploring the Role of DKK1 in the Occurrence of Lung Adenocarcinoma Based on the Analysis of Bioinformatics].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Article
- Single-cell characteristics and malignancy regulation of alpha-fetoprotein-producing gastric cancer.Cancer medicine · 2023Article
- Review
- DKK1 drives immune suppressive phenotypes in intrahepatic cholangiocarcinoma and can be targeted with anti-DKK1 therapeutic DKN-01.Liver international : official journal of the International Association for the Study of the Liver · 2023Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND AND
aimsDickkopf-1 (DKK1) is associated with poor prognosis in intrahepatic cholangiocarcinoma (iCCA), but the mechanisms behind this are unclear. Here, we show that DKK1 plays an immune regulatory role in vivo and inhibition reduces tumour growth.
methodsVarious in vivo GEMM mouse models and patient samples were utilized to assess the effects of tumour specific DKK1 overexpression in iCCA. DKK1-driven changes to the tumour immune microenvironment were characterized by immunostaining and gene expression analysis. DKK1 overexpressing and damage-induced models of iCCA were used to demonstrate the therapeutic efficacy of DKK1 inhibition in these contexts using the anti-DKK1 therapeutic, DKN-01.
resultsDKK1 overexpression in mouse models of iCCA drives an increase in chemokine and cytokine signalling, the recruitment of regulatory macrophages, and promotes the formation of a tolerogenic niche with higher numbers of regulatory T cells. We show a similar association of DKK1 with FOXP3 and regulatory T cells in patient tissue and gene expression data, demonstrating these effects are relevant to human iCCA. Finally, we demonstrate that inhibition of DKK1 with the monoclonal antibody mDKN-01 is effective at reducing tumour burden in two distinct mouse models of the disease.
conclusionDKK1 promotes tumour immune evasion in iCCA through the recruitment of immune suppressive macrophages. Targeting DKK1 with a neutralizing antibody is effective at reducing tumour growth in vivo. As such, DKK1 targeted and immune modulatory therapies may be an effective strategy in iCCA patients with high DKK1 tumour expression or tolerogenic immune phenotypes.
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