Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice
Top Cited Papers
- 11 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Microbiology
- Vol. 6 (3), 277-288
- https://doi.org/10.1038/s41564-020-00831-6
Abstract
The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1,2,3,4,5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites.Keywords
Funding Information
- Ministry of Trade, Industry and Energy (10067758)
- National Research Foundation of Korea (NRF-2018M3A9F3056902, 2018R1C1B6005768, NRF-2018R1A2A1A05019794, 2015K1A4A3047851, 2017R1C1B2011196, NRF-2017M3A9F304636)
- Ewha Womans University (2017-2019)
- Xi'an Jiaotong University
- Ministry of Health and Welfare (HI17C1076)
- National Cancer Center (NCC-1911267)
- Gwangju Institute of Science and Technology (GIST Research Institute (GRI))
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