ArticleCancer immunology research2015
Melanoma-Derived Wnt5a Promotes Local Dendritic-Cell Expression of IDO and Immunotolerance: Opportunities for Pharmacologic Enhancement of Immunotherapy.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
120 citing papers in PubMed, 178 citations in OpenAlex.
- Role of the Wnt5A pathway in resistance to immune checkpoint inhibitors in advanced Non-Small Cell Lung Cancer.Cancer immunology, immunotherapy : CII · 2026Article
- From Immunobiology to Clinical Application: Tumor-Infiltrating Lymphocytes in Melanoma.Journal of personalized medicine · 2026Review
- Rewiring Dendritic Cell Immunity: The β-Catenin-TIM-3 Axis as a Target to Improve DC Cancer Vaccines.Cancers · 2026Review
- Targeted protein degradation of Wnt/β-catenin signaling pathway: an effective strategy for cancer therapy.Journal of translational medicine · 2025Review
- Balancing Immunity: GSK-3's Divergent Roles in Dendritic Cell-Mediated T-Cell Priming and Memory Responses.International journal of molecular sciences · 2025Review
- Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors.Pharmaceutics · 2025Article
- GLI2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating WNT and Prostaglandin Signaling.Cancer research · 2025Article
- A new era in melanoma immunotherapy: focus on DCs metabolic reprogramming.Cancer cell international · 2025Review
- Gut microbiota affects PD-L1 therapy and its mechanism in melanoma.Cancer immunology, immunotherapy : CII · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Immune checkpoint blockade for cancer therapy: current progress and perspectives.Journal of Zhejiang University. Science. B · 2025Review
- Targeting Wnt-driven metabolic adaptations in cancer: integrating glycolysis, glutaminolysis, IDO1-mediated immune evasion, and therapeutic delivery strategies.Frontiers in cell and developmental biology · 2025Review
- Therapeutic Potential of Natural Compounds to Modulate WNT/β-Catenin Signaling in Cancer: Current State of Art and Challenges.International journal of molecular sciences · 2024Review
- The mitochondrial stress signaling tunes immunity from a view of systemic tumor microenvironment and ecosystem.iScience · 2024Review
- Genomic and molecular alterations associated with primary resistance to immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2024Review
- Article
- MerTK Induces Dysfunctional Dendritic Cells by Metabolic Reprogramming.Cancer immunology research · 2024Article
- Developing Engineered Nano-Immunopotentiators for the Stimulation of Dendritic Cells and Inhibition and Prevention of Melanoma.Pharmaceutical research · 2024Article
- A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression.Science immunology · 2024Article
- β-Catenin in Dendritic Cells Negatively Regulates CD8 T Cell Immune Responses through the Immune Checkpoint Molecule Tim-3.Vaccines · 2024Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The β-catenin signaling pathway has been demonstrated to promote the development of a tolerogenic dendritic cell (DC) population capable of driving regulatory T-cell (Treg) differentiation. Further studies have implicated tolerogenic DCs in promoting carcinogenesis in preclinical models. The molecular mechanisms underlying the establishment of immune tolerance by this DC population are poorly understood, and the methods by which developing cancers can co-opt this pathway to subvert immune surveillance are currently unknown. This work demonstrates that melanoma-derived Wnt5a ligand upregulates the durable expression and activity of the indoleamine 2,3-dioxygenase-1 (IDO) enzyme by local DCs in a manner that depends upon the β-catenin signaling pathway. These data indicate that Wnt5a-conditioned DCs promote the differentiation of Tregs in an IDO-dependent manner, and that this process serves to suppress melanoma immune surveillance. We further show that the genetic silencing of the PORCN membrane-bound O-acyl transferase, which is necessary for melanoma Wnt ligand secretion, enhances antitumor T-cell immunity, and that the pharmacologic inhibition of this enzyme synergistically suppresses melanoma progression when combined with anti-CTLA-4 antibody therapy. Finally, our data suggest that β-catenin signaling activity, based on a target gene expression profile that includes IDO in human sentinel lymph node-derived DCs, is associated with melanoma disease burden and diminished progression-free survival. This work implicates the Wnt-β-catenin signaling pathway as a novel therapeutic target in the melanoma immune microenvironment and demonstrates the potential impact of manipulating DC function as a strategy for optimizing tumor immunotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.