Dietary<i>Lactobacillus</i>-Derived Exopolysaccharide Enhances Immune-Checkpoint Blockade Therapy
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- Hirotaka Kawanabe-Matsuda
- 1Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
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- Kazuyoshi Takeda
- 1Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
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- Marie Nakamura
- 2Research Team, Co-Creation Center, Meiji Holdings Co., Ltd., Hachioji, Japan.
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- Seiya Makino
- 1Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
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- Takahiro Karasaki
- 4Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo, Japan.
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- Kazuhiro Kakimi
- 4Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo, Japan.
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- Megumi Nishimukai
- 6Department of Animal Science, Faculty of Agriculture, Iwate University, Morioka, Japan.
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- Tatsukuni Ohno
- 1Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
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- Jumpei Omi
- 9Department of Health Chemistry, Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo, Japan.
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- Kuniyuki Kano
- 9Department of Health Chemistry, Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo, Japan.
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- Akiharu Uwamizu
- 9Department of Health Chemistry, Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo, Japan.
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- Hideo Yagita
- 12Department of Immunology, School of Medicine, Juntendo University, Tokyo, Japan.
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- Ivo Gomperts Boneca
- 13Institut Pasteur, Unit of Biology and Genetics of Bacterial Cell Wall, Paris, France. INSERM, Équipe Avenir, Paris, France.
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- Gérard Eberl
- 14Microenvironment and Immunity Unit, Institut Pasteur, Paris, France.
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- Junken Aoki
- 9Department of Health Chemistry, Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo, Japan.
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- Mark J. Smyth
- 15Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
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- Ko Okumura
- 1Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
説明
<jats:title>Abstract</jats:title><jats:sec><jats:title/><jats:p>Microbes and their byproducts have been reported to regulate host health and immune functions. Here we demonstrated that microbial exopolysaccharide produced by Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (EPS-R1) induced CCR6+ CD8+ T cells of mice and humans. In mice, ingestion of EPS-R1 augmented antitumor effects of anti–CTLA-4 or anti–PD-1 monoclonal antibody against CCL20-expressing tumors, in which infiltrating CCR6+ CD8+ T cells were increased and produced IFNγ accompanied by a substantial immune response gene expression signature maintaining T-cell functions. Of note, the antitumor adjuvant effect of EPS-R1 was also observed in germ-free mice. Furthermore, the induction of CCR6 expression was mediated through the phosphorylated structure in EPS-R1 and a lysophosphatidic acid receptor on CD8+ T cells. Overall, we find that dietary EPS-R1 consumption induces CCR6+ CD8+ T cells in Peyer's patches, favoring a tumor microenvironment that augments the therapeutic effect of immune-checkpoint blockade depending on CCL20 production by tumors.</jats:p></jats:sec><jats:sec><jats:title>Significance:</jats:title><jats:p>Gut microbiota- and probiotic-derived metabolites are attractive agents to augment the efficacy of immunotherapies. Here we demonstrated that dietary consumption of Lactobacillus-derived exopolysaccharide induced CCR6+ CD8+ T cells in Peyer's patches and improved the tumor microenvironment to augment the therapeutic effects of immune-checkpoint blockade against CCL20-producing tumors.</jats:p><jats:p>See related commentary by Di Luccia and Colonna, p. 1189.</jats:p><jats:p>This article is highlighted in the In This Issue feature, p. 1171</jats:p></jats:sec>
収録刊行物
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- Cancer Discovery
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Cancer Discovery 12 (5), 1336-1355, 2022-02-17
American Association for Cancer Research (AACR)
