Cited by 288Cancer Immunotherapy and BiomarkersGut microbiota and healthImmunotherapy and Immune Responses

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Generation of systemic antitumour immunity via the in situ modulation of the gut microbiome by an orally administered inulin gel

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Han, Kai, Nam, Jutaek, Xu, Jin, Sun, Xiaoqi, Huang, Xuehui, Animasahun, Olamide, Achreja, Abhinav, Jeon, Jin Heon, Pursley, Benjamin, Kamada, Nobuhiko, Chen, Grace Y., Nagrath, Deepak, Moon, James J.·2021·Nature Biomedical Engineering

DOI 10.1038/s41551-021-00749-2PMC PMC8595497

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Abstract

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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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: Han, Kai
Nam, Jutaek
Xu, Jin
Sun, Xiaoqi
Huang, Xuehui
Animasahun, Olamide
Achreja, Abhinav
Jeon, Jin Heon
Kamada, Nobuhiko
Chen, Grace Y.
Nagrath, Deepak
Moon, James J.
Venue: Nature Biomedical Engineering
Publisher: Springer Science and Business Media LLC
Published: 2021-06-24
Volume: 5
Issue: 11
Pages: 1377-1388
ISSN: 2157-846X (ISSN-L)
DOI: 10.1038/s41551-021-00749-2
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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Generation of systemic antitumour immunity via the in situ modulation of the gut microbiome by an orally administered inulin gel

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