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Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer.
World J Gastroenterol. 2016 Jan 14; 22(2):557-66.WJ

Abstract

The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum (F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6% (44/511), which was lower than that in United States cohort studies (13%). Similar to the United States studies, F. nucleatum positivity in Japanese colorectal cancers was significantly associated with microsatellite instability (MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets (i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain microRNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. MicroRNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and microRNA expressions in colorectal cancer.

Authors+Show Affiliations

Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.Katsuhiko Nosho, Yasutaka Sukawa, Yasushi Adachi, Miki Ito, Kei Mitsuhashi, Hiroyoshi Kurihara, Shinichi Kanno, Itaru Yamamoto, Keisuke Ishigami, Hisayoshi Igarashi, Yasuhisa Shinomura, Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26811607

Citation

Nosho, Katsuhiko, et al. "Association of Fusobacterium Nucleatum With Immunity and Molecular Alterations in Colorectal Cancer." World Journal of Gastroenterology, vol. 22, no. 2, 2016, pp. 557-66.
Nosho K, Sukawa Y, Adachi Y, et al. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J Gastroenterol. 2016;22(2):557-66.
Nosho, K., Sukawa, Y., Adachi, Y., Ito, M., Mitsuhashi, K., Kurihara, H., Kanno, S., Yamamoto, I., Ishigami, K., Igarashi, H., Maruyama, R., Imai, K., Yamamoto, H., & Shinomura, Y. (2016). Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World Journal of Gastroenterology, 22(2), 557-66. https://doi.org/10.3748/wjg.v22.i2.557
Nosho K, et al. Association of Fusobacterium Nucleatum With Immunity and Molecular Alterations in Colorectal Cancer. World J Gastroenterol. 2016 Jan 14;22(2):557-66. PubMed PMID: 26811607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. AU - Nosho,Katsuhiko, AU - Sukawa,Yasutaka, AU - Adachi,Yasushi, AU - Ito,Miki, AU - Mitsuhashi,Kei, AU - Kurihara,Hiroyoshi, AU - Kanno,Shinichi, AU - Yamamoto,Itaru, AU - Ishigami,Keisuke, AU - Igarashi,Hisayoshi, AU - Maruyama,Reo, AU - Imai,Kohzoh, AU - Yamamoto,Hiroyuki, AU - Shinomura,Yasuhisa, PY - 2015/06/30/received PY - 2015/09/25/revised PY - 2015/11/13/accepted PY - 2016/1/27/entrez PY - 2016/1/27/pubmed PY - 2017/1/18/medline KW - BRAF KW - Colon neoplasia KW - CpG island methylator phenotype KW - Fusobacterium species KW - miR-21 SP - 557 EP - 66 JF - World journal of gastroenterology JO - World J Gastroenterol VL - 22 IS - 2 N2 - The human intestinal microbiome plays a major role in human health and diseases, including colorectal cancer. Colorectal carcinogenesis represents a heterogeneous process with a differing set of somatic molecular alterations, influenced by diet, environmental and microbial exposures, and host immunity. Fusobacterium species are part of the human oral and intestinal microbiota. Metagenomic analyses have shown an enrichment of Fusobacterium nucleatum (F. nucleatum) in colorectal carcinoma tissue. Using 511 colorectal carcinomas from Japanese patients, we assessed the presence of F. nucleatum. Our results showed that the frequency of F. nucleatum positivity in the Japanese colorectal cancer was 8.6% (44/511), which was lower than that in United States cohort studies (13%). Similar to the United States studies, F. nucleatum positivity in Japanese colorectal cancers was significantly associated with microsatellite instability (MSI)-high status. Regarding the immune response in colorectal cancer, high levels of infiltrating T-cell subsets (i.e., CD3+, CD8+, CD45RO+, and FOXP3+ cells) have been associated with better patient prognosis. There is also evidence to indicate that molecular features of colorectal cancer, especially MSI, influence T-cell-mediated adaptive immunity. Concerning the association between the gut microbiome and immunity, F. nucleatum has been shown to expand myeloid-derived immune cells, which inhibit T-cell proliferation and induce T-cell apoptosis in colorectal cancer. This finding indicates that F. nucleatum possesses immunosuppressive activities by inhibiting human T-cell responses. Certain microRNAs are induced during the macrophage inflammatory response and have the ability to regulate host-cell responses to pathogens. MicroRNA-21 increases the levels of IL-10 and prostaglandin E2, which suppress antitumor T-cell-mediated adaptive immunity through the inhibition of the antigen-presenting capacities of dendritic cells and T-cell proliferation in colorectal cancer cells. Thus, emerging evidence may provide insights for strategies to target microbiota, immune cells and tumor molecular alterations for colorectal cancer prevention and treatment. Further investigation is needed to clarify the association of Fusobacterium with T-cells and microRNA expressions in colorectal cancer. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/26811607/Association_of_Fusobacterium_nucleatum_with_immunity_and_molecular_alterations_in_colorectal_cancer_ L2 - https://www.wjgnet.com/1007-9327/full/v22/i2/557.htm DB - PRIME DP - Unbound Medicine ER -