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Generation of systemic antitumour immunity via the in situ modulation of the gut microbiome by an orally administered inulin gel
Open accessAbstract
The performance of immune-checkpoint inhibitors, which benefit only a subset of patients and can cause serious immune-related adverse events, underscores the need for strategies that induce T-cell immunity with minimal toxicity. The gut microbiota has been implicated in the outcomes of patients following cancer immunotherapy, yet manipulating the gut microbiome to achieve systemic antitumour immunity is challenging. Here we show in multiple murine tumour models that inulin-a widely consumed dietary fibre-formulated as a 'colon-retentive' orally administered gel can effectively modulate the gut microbiome in situ, induce systemic memory-T-cell responses and amplify the antitumour activity of the checkpoint inhibitor anti-programmed cell death protein-1 (α-PD-1). Orally delivered inulin-gel treatments increased the relative abundances of key commensal microorganisms and their short-chain-fatty-acid metabolites, and led to enhanced recall responses for interferon-γ+CD8+ T cells as well as to the establishment of stem-like T-cell factor-1+PD-1+CD8+ T cells within the tumour microenvironment. Gels for the in situ modulation of the gut microbiome may be applicable more broadly to treat pathologies associated with a dysregulated gut microbiome.
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“This gel has the propensity to reformulate the composition of the gut microbiota and its metabolic outputs, consequently invigorating the immune system and potentiating an antitumor-immune response.224”
From Drug repurposing for cancer therapy (2024) · cites this paper as [224]
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“Intriguingly, experimental studies on animal models have revealed that oral administration of inulin gel significantly amplifies the efficacy of immune checkpoint therapy while maintaining an admirable safety profile.”
From Drug repurposing for cancer therapy (2024) · cites this paper as [224]
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“Prebiotics are a group of substances that can be used by host bacteria to enhance the proportion of beneficial species to improve the anti-tumor immunity13–15.”
From Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy (2023) · cites this paper as [15]
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“For instance, a mouse study showed that orally administered inulin induced memory T cell responses and improved responses to anti-PD-1 therapy (Han et al., 2021).”
From Microbiota-centered interventions to boost immune checkpoint blockade therapies (2025) · cites this paper as Han et al., 2021
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Metadata
- Authors
- Han, K., Nam, J., Xu, J., Sun, X., Huang, X., Animasahun, O., Achreja, A., Jeon, J. H., Pursley, B., Kamada, N., Chen, G. Y., Nagrath, D., & Moon, J. J.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Moon, James J.
- ORCID
- Venue
- Nature Biomedical Engineering
- Published
- 2021-06-24
- Volume
- 5
- Issue
- 11
- Pages
- 1377-1388
- ISSN
- 2157-846X (ISSN-L)
- PMC
- PMC8595497
- OpenAlex
- W3175731140
- Cited by
- 287
- References
- 41
- Citations by year
- 2026: 61 · 2025: 77 · 2024: 60 · 2023: 45 · 2022: 36 · 2021: 8
- FWCI
- 13.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R01AI127070)
- U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (R01EB022563)
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (R01DK125087)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- inulin, gut microbiota modulation, antitumor immunity, immune checkpoint inhibitors, anti-PD-1 therapy, dietary fiber, short-chain fatty acids, memory T cells, CD8+ T cells, tumor microenvironment, cancer immunotherapy, commensal bacteria
- MeSH terms
- Gastrointestinal Microbiome, Animals, Gels, Humans, Immunotherapy, Inulin, CD8-Positive T-Lymphocytes, Mice
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