ArticleCancer discovery2022
A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti-PD-1 Resistance through Effects on the Gut Microbiota.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06904573 (A Multicenter, Randomized Controlled Phase II Study of Evaluating the Efficacy and Safety of Immunotherapy Combined With Oral Probiotics Compound), which is not on this map. Cited by 142 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
A Multicenter, Randomized Controlled Phase II Study of Evaluating the Efficacy and Safety of Immunotherapy Combined With Oral Probiotics Compound (Biolosion) in Patients With Advanced Urothelial Carcinoma
Who cites it
142 citing papers in PubMed, 2 syntheses or guidelines pooled it, 213 citations in OpenAlex.
- A bibliometric study on the impact of gut microbiota on the efficacy of immune checkpoint inhibitors in cancer patients: analysis of the top 100 cited articles.Frontiers in immunology · 2024Pooled it
- Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy.Nature reviews. Clinical oncology · 2023Pooled it
- Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial.Nature medicine · 2026Trial
- The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers.Nature communications · 2024Trial
- Camu-camu decreases hepatic steatosis and liver injury markers in overweight, hypertriglyceridemic individuals: A randomized crossover trial.Cell reports. Medicine · 2024Trial
- Dietary intervention through bacterial-derived butyrate elicits anti-tumor activity and increases anti-PD-1 response.Gut microbes · 2026Article
- PD-1 blockade promotes mucosal CD4+ T cell IL-10 production through altering microbiota to reduce intestinal ischemia reperfusion injury.Gut microbes · 2026Article
- The impact of gut microbiota and metabolite-driven immune cell spatiotemporal dynamics on tumors.Gut microbes · 2026Review
- Molecular pathways linking the gut microbiome to antitumor immunity.Trends in microbiology · 2026Review
- Gut microbiota alterations in patients with non-small-cell lung cancer undergoing chemoradiotherapy.Molecular oncology · 2026Article
- Mechanistic Links Between Natural Bioactive Molecules and Tumor Immune Microenvironment States in PD-1/PD-L1 Resistance.Biomedicines · 2026Review
- Microbiome-Shaped Metastatic Niches in Colorectal Cancer: Organ-Specific Patterns, Immune-Metabolic Mechanisms, and Therapeutic Translation.Microorganisms · 2026Review
- Phytochemicals remodel antitumor immunity via the "microbiota-metabolite-receptor" axis: focus on colorectal cancer and immunotherapy.Medical oncology (Northwood, London, England) · 2026Review
- Regulation of PD-1PD-L1 Immune Checkpoints by Gut Microbiota Metabolites and Their Clinical Translational Research: A Review.Immunity, inflammation and disease · 2026Review
- Leveraging gut microbiota for enhanced immune checkpoint blockade in solid tumor therapy.Chinese medical journal · 2026Review
- Harnessing the microbiome for cancer therapy.Nature reviews. Microbiology · 2026Review
- Harnessing Gut Microbiota to Enhance Immunotherapy in NSCLC: From Mechanisms to Translational Applications.Cancer medicine · 2026Review
- Role of gut microbiota in cancer modulation: molecular mechanisms and emerging therapeutic strategies.Infectious agents and cancer · 2026Review
- Article
- Microbiota-derived metabolites as modulators of cancer immunotherapy response.Nature communications · 2026Review
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 12 institutions in 4 countries.
Funding
Abstract
Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/FOXP3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine-conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance. SIGNIFICANCE: The polyphenol castalagin isolated from a berry has an antitumor effect through direct interactions with commensal bacteria, thus reprogramming the tumor microenvironment. In addition, in preclinical ICI-resistant models, castalagin reestablishes the efficacy of anti-PD-1. Together, these results provide a strong biological rationale to test castalagin as part of a clinical trial. This article is highlighted in the In This Issue feature, p. 873.
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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.