ArticleCancer science2022
Stemness and immune evasion conferred by the TDO2-AHR pathway are associated with liver metastasis of colon cancer.
Article in Cancer science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 50 citations in OpenAlex.
- Microbiome-Shaped Metastatic Niches in Colorectal Cancer: Organ-Specific Patterns, Immune-Metabolic Mechanisms, and Therapeutic Translation.Microorganisms · 2026Review
- The Oncogenic Role of Prostate Stem Cell Antigen (PSCA) in Colorectal Cancer: Implications for Targeted Therapy.Current issues in molecular biology · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Regulation of PD-1PD-L1 Immune Checkpoints by Gut Microbiota Metabolites and Their Clinical Translational Research: A Review.Immunity, inflammation and disease · 2026Review
- Review
- The aryl hydrocarbon receptor: structure, signaling, physiology and pathology.Signal transduction and targeted therapy · 2026Review
- Emerging nano-immunotherapeutic strategies achieve metastatic colorectal cancer precision therapy.Journal of nanobiotechnology · 2026Review
- Gut microbial metabolites in colorectal cancer: dual roles in tumorigenesis, immune crosstalk, and therapeutic innovation.Frontiers in cellular and infection microbiology · 2026Review
- Investigating tryptophan metabolism in colorectal cancer using Single-cell RNA sequencing based on machine learning techniques.PloS one · 2026Article
- Tryptophan metabolism in tumor immune escape: mechanisms, cellular crosstalk, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Context-dependent functions of the aryl hydrocarbon receptor in gastrointestinal cancers: from microenvironmental regulation to precision targeted therapy.Frontiers in cell and developmental biology · 2026Review
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- Role of Tryptophan Metabolism in Cancer.Cancer innovation · 2025Review
- Cancer Stem Cells Connecting to Immunotherapy: Key Insights, Challenges, and Potential Treatment Opportunities.Cancers · 2025Review
- The aryl hydrocarbon receptor: a new frontier in male reproductive system.Reproductive biology and endocrinology : RB&E · 2025Review
- Review
- Targeting the Kynurenine Pathway: A Novel Approach in Tumor Therapy.Expert reviews in molecular medicine · 2025Review
- Cancer stem cells and niches: challenges in immunotherapy resistance.Molecular cancer · 2025Review
- Role of Kynurenine and Its Derivatives in Liver Diseases: Recent Advances and Future Clinical Perspectives.International journal of molecular sciences · 2025Review
- TDO2 + cancer-associated fibroblasts mediate cutaneous squamous cell carcinoma immune escape via impeding infiltration of CD8 + T cells.Cancer immunology, immunotherapy : CII · 2025Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The aryl hydrocarbon receptor (AHR) pathway modulates the immune system in response to kynurenine, an endogenous tryptophan metabolite. IDO1 and TDO2 catalyze kynurenine production, which promotes cancer progression by compromising host immunosurveillance. However, it is unclear whether the AHR activation regulates the malignant traits of cancer such as metastatic capability or cancer stemness. Here, we carried out systematic analyses of metabolites in patient-derived colorectal cancer spheroids and identified high levels of kynurenine and TDO2 that were positively associated with liver metastasis. In a mouse colon cancer model, TDO2 expression substantially enhanced liver metastasis, induced AHR-mediated PD-L1 transactivation, and dampened immune responses; these changes were all abolished by PD-L1 knockout. In patient-derived cancer spheroids, TDO2 or AHR activity was required for not only the expression of PD-L1, but also for cancer stem cell (CSC)-related characteristics and Wnt signaling. TDO2 was coexpressed with both PD-L1 and nuclear β-catenin in colon xenograft tumors, and the coexpression of TDO2 and PD-L1 was observed in clinical colon cancer specimens. Thus, our data indicate that the activation of the TDO2-kynurenine-AHR pathway facilitates liver metastasis of colon cancer via PD-L1-mediated immune evasion and maintenance of stemness.
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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.