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Fusobacterium nucleatum and the Immune System in Colorectal Cancer

  • Nutrition and Nutritional Interventions in Colorectal Cancer (K Wu, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Purpose of Review

To summarize the relationship between colorectal cancer (CRC), immunity, and the gut microbiome, focusing on the population of Fusobacterium, particularly Fusobacterium nucleatum, which may mediate CRC initiation and progression by inhibiting host anti-tumor immunity.

Recent Findings

The onset and advancement of CRC involves genetic and epigenetic alterations and are modified by dietary and environmental factors. There is increasing evidence suggesting that gut bacteria, such as Fusobacterium nucleatum, may promote CRC development. The mechanisms through which Fusobacterium nucleatum from the oral cavity colonizes the gut mucosa and affect CRC development and progression remain unclear. Data from metagenomics analyses have shown an enrichment of Fusobacterium nucleatum in CRC tissues, which has been confirmed by quantitative PCR for the 16S ribosomal RNA gene DNA sequence of Fusobacterium nucleatum. Recent studies also suggest that Fusobacterium nucleatum may preferentially bind to cancerous cells, aided by Annexin A1, specifically expressed in proliferating CRC cells. This is consistent with a previous report that although Fusobacterium nucleatum is detected in both colorectal adenoma and adenocarcinoma tissues, the fadA gene levels are significantly higher in the latter than in the former. Other potential mechanisms include the ability of Fusobacterium to produce cancer-associated metabolites or genotoxic factors and possibly a direct interaction with the host immune system. Supporting a possible interaction with the host immune system are recent data indicating that overload of Fusobacterium nucleatum elicits high levels of Fusobacterium nucleatum-specific antibodies in CRC patients, suggesting that Fusobacterium nucleatum may escape host humoral immune responses by evolving inside host cells. Additionally, it has been found that the interaction of Fusobacterium nucleatum with immune response to CRC differs by tumor microsatellite (MS) status, suggesting that Fusobacterium nucleatum and MS status interact to influence anti-tumor immune functions.

Summary

The current literature suggests that Fusobacterium nucleatum, a Gram-negative oral anaerobe, may significantly contribute to CRC development. Furthermore, the presence of Fusobacterium nucleatum in CRCs has also been associated with MSI-high status, lower levels of infiltrating T-lymphocytes, and poor clinical outcomes. We believe that the integration of new technologies, including genomics, bioinformatics and systems medicine, may help to better understand how Fusobacterium nucleatum, immunity status, and environmental factors interact in the initiation and progression of CRCs and generate further information regarding prognostic and therapeutics options for this tumor.

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Acknowledgments

The authors are grateful to Teri Field for her editorial support.

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Authors and Affiliations

  1. Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy

    Elena Monica Borroni & Floriana Maria Farina

  2. Department of Leukocyte Biology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Elena Monica Borroni & Floriana Maria Farina

  3. Department of Immunology and Inflammation, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy

    Dorina Qehajaj & Fabio Grizzi

  4. Department of General Surgery, Frimley Health NHS Foundation Trust, Wexham Park, Wexham Street, Slough, UK

    Daniel Yiu

  5. Department of Gastroenterology, Hepatology and Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Robert S. Bresalier & Maurizio Chiriva-Internati

  6. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Maurizio Chiriva-Internati

  7. Kiromic Inc., Houston, TX, USA

    Maurizio Chiriva-Internati & Leonardo Mirandola

  8. Department of Pathology, Clinical Hospital Center Rijeka, Rijeka, Croatia

    Sanja Štifter

  9. Department of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Luigi Laghi

  10. Hereditary Cancer Genetics Clinic, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Luigi Laghi

  11. Histology Core, Humanitas Clinical and Research Center, Rozzano, Milan, Italy

    Fabio Grizzi

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  1. Elena Monica Borroni
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Contributions

Borroni EM, Qehajaj D, Farina FM, Yiu D, Bresalier RS, Chiriva-Internati M, Mirandola L, Stifter S, Laghi L, Grizzi F: drafted and discussed the manuscript and approved the final version.

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Correspondence to Fabio Grizzi.

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Borroni, E.M., Qehajaj, D., Farina, F.M. et al. Fusobacterium nucleatum and the Immune System in Colorectal Cancer. Curr Colorectal Cancer Rep 15, 149–156 (2019). https://doi.org/10.1007/s11888-019-00442-2

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  • DOI: https://doi.org/10.1007/s11888-019-00442-2

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