ArticleNature communications2022
Ursodeoxycholic acid reduces antitumor immunosuppression by inducing CHIP-mediated TGF-β degradation.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- The Clinical Impact of Time-restricted Eating on Cancer: A Systematic Review.Nutrition reviews · 2025Pooled it
- Tropomyosin-1 positively regulates TGF-β/Smad3 signaling through STUB1 in arecoline-induced oral submucosal fibrosis.Odontology · 2026Article
- Lactobacillus salivarius potentiates gastrointestinal cancer immunotherapy through its metabolite chenodeoxycholic acid.Cell reports. Medicine · 2026Article
- Oral nano-delivery of a gut microbial metabolite enhances T cell stemness for cancer immunotherapy.Nature nanotechnology · 2026Article
- Advances in Exercise-Mediated Regulation of the Gut Microbiota via the Muscle-Gut Axis: Implications for Tumor Immunity and Treatment Responses.Metabolites · 2026Review
- Chenodeoxycholic acid restrains tumor growth via TGR5-dependent type 1 dendritic cells cross-priming.Signal transduction and targeted therapy · 2026Article
- The dual role of gastric microbiota dysbiosis in gastric cancer progression and therapy.International journal of clinical oncology · 2026Review
- EGR1 Mediates Ursodeoxycholic Acid-Promoted Mitophagy to Prevent Postovulatory Aging of Porcine Oocytes.Aging cell · 2026Article
- Decoding the microbiome-immune crosstalk in cancer: from mechanisms to therapeutic translation.Biomarker research · 2026Review
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Elevated lactate production exacerbates PM2.5-induced pulmonary fibrosis by stabilizing TGF-β1.Journal of advanced research · 2026Article
- Probiotics Cancer Interaction, Prevention, and Therapy.Immunity, inflammation and disease · 2026Review
- The conjugation-resistant bile acid norUDCA cures liver fibrosis but impairs systemic energy metabolism.Molecular metabolism · 2026Article
- Anti-Cancer Effects of Quercetin: What Role Does the Gut Microbiota Play?Molecules (Basel, Switzerland) · 2026Review
- Microbiota-derived metabolites as modulators of cancer immunotherapy response.Nature communications · 2026Review
- Gut Microbiota Biomarkers in Patients with Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors.Life (Basel, Switzerland) · 2026Review
- Targeting the gut microbiota-metabolite-immune axis in cancer immunotherapy: mechanistic interplay, therapeutic strategies, and translational applications-a narrative review.Translational cancer research · 2026Review
- Regulatory T cells in the breast cancer tumor microenvironment: new mechanisms, potential therapeutic strategies and future perspectives.American journal of cancer research · 2026Review
- Medicago Sativa L. Saponin-Driven Lactobacillus Intestinalis Restores Intestinal Stemness in Naturally Aged Mice via the Bile Acid-FXR-Wnt Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.Theranostics · 2026Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β is essential for inducing systemic tumor immunosuppression; thus, blocking TGF-β can greatly enhance antitumor immunity. However, there are still no effective TGF-β inhibitors in clinical use. Here, we show that the clinically approved compound ursodeoxycholic acid (UDCA), by degrading TGF-β, enhances antitumor immunity through restraining Treg cell differentiation and activation in tumor-bearing mice. Furthermore, UDCA synergizes with anti-PD-1 to enhance antitumor immunity and tumor-specific immune memory in tumor-bearing mice. UDCA phosphorylates TGF-β at T282 site via TGR5-cAMP-PKA axis, causing increased binding of TGF-β to carboxyl terminus of Hsc70-interacting protein (CHIP). Then, CHIP ubiquitinates TGF-β at the K315 site, initiating p62-dependent autophagic sorting and subsequent degradation of TGF-β. Notably, results of retrospective analysis shows that combination therapy with anti-PD-1 or anti-PD-L1 and UDCA has better efficacy in tumor patients than anti-PD-1 or anti-PD-L1 alone. Thus, our results show a mechanism for TGF-β regulation and implicate UDCA as a potential TGF-β inhibitor to enhance antitumor immunity.
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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.