ArticleCancer discovery2025
Gut Microbiota Modulation through Akkermansia spp. Supplementation Increases CAR T-cell Potency.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
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Who cites it
26 citing papers in PubMed.
- Associations Between Gut Microbiota and Immune Profiles in Community-Dwelling Older Adults and the Regulatory Role of Polygonatum odoratum.Aging cell · 2026Trial
- Adjuvant penpulimab in very-high risk clear cell renal cell carcinoma: a prospective, non-randomized, controlled phase II trial with integrated plasma multi-omics analyses.Journal for immunotherapy of cancer · 2026Trial
- Towards optimizing the host response to biotics: a report of an International Scientific Association for Probiotics and Prebiotics working group.Gut microbes · 2026Article
- Metabolic profiling of CAR T-cells in patients reveals a shift toward amino acid-supported OXPHOS and informs transporter engineering.Research square · 2026Article
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Gut microbiota modulation of gastrointestinal cancers: from dysbiosis signatures to therapeutic interventions.Acta pharmacologica Sinica · 2026Review
- Potential role of Akkermansia massiliensis in multiple sclerosis protection by the FcRL3 gene.Genes and immunity · 2026Article
- Colon-targeting pH-responsive Bletilla striata polysaccharide coacervate microdroplets for ulcerative colitis therapy via macrophage reprogramming.Journal of nanobiotechnology · 2026Article
- Therapeutic Potential of Polysaccharide-Modulated Gut Microbiota-Immune Axis in Gastrointestinal Cancers: Modern Insights From Traditional Pharmacy.Molecular nutrition & food research · 2026Review
- Icariin Enhances the Enzymatic Activity of N-acetylgalactosaminidase to Augment Akkermansia Abundance in Gut Microbiota for Improved PD-1 Blockade Efficacy in Tumor Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Harnessing the microbiome for cancer therapy.Nature reviews. Microbiology · 2026Review
- The mycobiome, virome and archaeome in gastrointestinal cancers: molecular pathogenesis and therapeutic intervention.Molecular cancer · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Decoding the microbiome-immune crosstalk in cancer: from mechanisms to therapeutic translation.Biomarker research · 2026Review
- Microbiota-derived metabolites as modulators of cancer immunotherapy response.Nature communications · 2026Review
- Biomarker-empowered precision navigation of CAR-T cell therapy.Molecular cancer · 2026Review
- Gut dysbiosis in oncology: a risk factor for immunoresistance.Cell research · 2026Review
- Soluble MAdCAM-1 as a biomarker in metastatic renal cell carcinoma.Nature medicine · 2026Article
- The Potential of the Gut Microbiota and Butyrate to Enhance CAR T-cell Therapy in Non-Hodgkin Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Microbiota-derived metabolic priming of CAR-T cell fitness: a translational framework for next-generation cell therapy.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
36 authors.
Funding
Abstract
This study investigates the clinical relevance of the gut microbiome at taxonomic and metabolic levels in anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, both in patients and in a preclinical syngeneic tumor model. Patients with B-cell lymphoma treated with CD19 CAR T cells exhibited profound intestinal dysbiosis, exacerbated after CAR T-cell infusion. This dysbiosis was characterized by low bacterial richness, low soluble MAdCAM-1, and loss of Akkermansia species, associated with resistance to therapy. Mechanistically, oral Akkermansia massiliensis supplementation increased CAR T-cell infiltration into the bone marrow, inverted the CD4/CD8 CAR T-cell ratio, favored Tc1 CD8+ T-cell polarization, and promoted the release of tryptophan-derived indole metabolites, leading to better tumor control. The clinical benefit of Akkermansia spp. supplementation was abolished when CAR T cells were genetically deficient in the indole receptor, aryl hydrocarbon receptor (AhR). AhR-agonistic indoles alone failed to replicate the bacterium's anticancer effects. These findings suggest that Akkermansia supplementation could improve CAR T-cell potency in patients with intestinal Akkermansia deficiency. SIGNIFICANCE: B-cell lymphoma patients treated with CAR T cells harbor major gut microbiota perturbations and related metabolism that restrain CAR T-cell therapy. Reprogramming the gut microbiota ecosystem by oral A. massiliensis supplementation induces CAR T-cell niching and Tc1 differentiation in the bone marrow, promoting tumor control in an AhR-dependent manner.
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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.