Cited by 116Cancer Immunotherapy and BiomarkersGut microbiota and healthT-cell and B-cell Immunology

Faecalibacterium prausnitzii Abrogates Intestinal Toxicity and Promotes Tumor Immunity to Increase the Efficacy of Dual CTLA4 and PD-1 Checkpoint Blockade

Gao, Yaqi, Xu, Pingping, Sun, Danfeng, Jiang, Yi, Lin, Xiao-Lin, Han, Ting, Yu, Jun, Sheng, Chunquan +5 more·2023·Cancer Research

Published version of a preprint

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy; however, their application is limited by the occurrence of immune-related adverse events. The gut microbiota plays important roles in the response to and toxicity of immunotherapy and Faecalibacterium prausnitzii (F. prausnitzii) has been shown to possess immunomodulatory potential. Here, we found that patients receiving ICIs who developed colitis had a lower abundance of F. prausnitzii. In vivo, immunocompetent mice administered with dextran sodium sulfate and immunodeficient NSG mice with human peripheral blood mononuclear cell transfer were treated with ICIs to study ICI-induced colitis. Dual CTLA4 and PD-1 blockade exacerbated autoimmune colitis, activated an inflammatory response, and promoted myeloid cell infiltration, with higher percentages of macrophages, dendritic cells, monocytes, and neutrophils. F. prausnitzii administration mitigated the exacerbated colitis induced by ICIs. Concomitantly, F. prausnitzii enhanced the antitumor immunity elicited by ICIs in tumor-bearing mice while abrogating colitis. In addition, administration of F. prausnitzii increased gut microbial alpha diversity and modulated the microbial composition, increasing a subset of gut probiotics and decreasing potential gut pathogens. F. prausnitzii abundance was reduced in mice that developed ICI-associated colitis. Together, this study shows that F. prausnitzii administration ameliorates ICI-induced colitis, reshapes the gut microbial composition, and enhances the antitumor activity of immunotherapy. SIGNIFICANCE: F. prausnitzii alleviates colitis while enhancing the tumor-suppressive effects of immune checkpoint blockade, indicating that supplementation with F. prausnitzii could be a treatment strategy to mitigate immunotherapy toxicity in patients with cancer.

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Crossref · 10.1158/0008-5472.can-23-0605

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Authors
Gao, Y., Xu, P., Sun, D., Jiang, Y., Lin, X.-L., Han, T., Yu, J., Sheng, C., Chen, H., Hong, J., Chen, Y., Xiao, X.-Y., & Fang, J.-Y.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • 2Department of Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Chinese University of Hong Kong (HK)
  • Second Military Medical University (CN)
Corresponding author
Fang, Jing-Yuan
Venue
Cancer Research
Published
2023-08-21
Volume
83
Issue
22
Pages
3710-3725
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W4386020321
Cited by
116
References
39
Citations by year
2026: 43 · 2025: 53 · 2024: 20
FWCI
14.09
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2020YFA0509200)
  • National Natural Science Foundation of China (81830081, 82250005, 31970718)
  • Innovative Research Team of High-level Local University in Shanghai (SSMU-ZLCX20180200)
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 › T-cell and B-cell Immunology
Keywords
Faecalibacterium prausnitzii, immune checkpoint inhibitors, CTLA-4 blockade, anti-PD-1 therapy, immune-related adverse events, gut microbiota, antitumor immunity, myeloid cell infiltration, microbial diversity, probiotics, DSS-induced colitis, NSG mice
MeSH terms
Faecalibacterium prausnitzii, Animals, Colitis, Humans, Leukocytes, Mononuclear, Neoplasms, Mice, CTLA-4 Antigen, Programmed Cell Death 1 Receptor

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