Fusobacterium nucleatum and the Immune System in Colorectal Cancer

  • Elena Monica Borroni
  • Dorina Qehajaj
  • Floriana Maria Farina
  • Daniel Yiu
  • Robert S. Bresalier
  • Maurizio Chiriva-Internati
  • Leonardo Mirandola
  • Sanja Štifter
  • Luigi Laghi
  • Fabio GrizziEmail author
Nutrition and Nutritional Interventions in Colorectal Cancer (K Wu, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Nutrition and Nutritional Interventions in Colorectal Cancer


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.


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.


Colorectal cancer Fusobacterium nucleatum Immunity Microbiome, diet 



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

Authors’ Contributors

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.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.Google Scholar
  2. 2.
    Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, et al. Colorectal cancer statistics, 2017. CA Cancer J Clin. 2017;67(3):177–93.Google Scholar
  3. 3.
    Pai RK, Bettington M, Srivastava A, Rosty C. An update on the morphology and molecular pathology of serrated colorectal polyps and associated carcinomas. Mod Pathol. 2019.
  4. 4.
    Nojadeh JN, Behrouz Sharif S, Sakhinia E. Microsatellite instability in colorectal cancer. EXCLI J. 2018;17:159–68.Google Scholar
  5. 5.
    Hughes LAE, Simons C, van den Brandt PA, van Engeland M, Weijenberg MP. Lifestyle, diet, and colorectal cancer risk according to (epi)genetic instability: current evidence and future directions of molecular pathological epidemiology. Curr Colorectal Cancer Rep. 2017;13(6):455–69.Google Scholar
  6. 6.
    Pino MS, Kikuchi H, Zeng M, Herraiz MT, Sperduti I, Berger D, et al. Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability. Gastroenterology. 2010;138(4):1406–17.Google Scholar
  7. 7.
    Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, et al. Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors. Gastroenterology. 2013;145(3):647–57 e615.Google Scholar
  8. 8.
    Liu Y, Baba Y, Ishimoto T, Iwatsuki M, Hiyoshi Y, Miyamoto Y, et al. Progress in characterizing the linkage between Fusobacterium nucleatum and gastrointestinal cancer. J Gastroenterol. 2019;54(1):33–41.Google Scholar
  9. 9.
    Liu L, Tabung FK, Zhang X, Nowak JA, Qian ZR, Hamada T, et al. Diets that promote colon inflammation associate with risk of colorectal carcinomas that contain Fusobacterium nucleatum. Clin Gastroenterol Hepatol. 2018;16(10):1622–31 e1623.Google Scholar
  10. 10.
    Farhana L, Banerjee HN, Verma M, Majumdar APN. Role of microbiome in carcinogenesis process and epigenetic regulation of colorectal cancer. Methods Mol Biol. 1856;2018:35–55.Google Scholar
  11. 11.
    Dahmus JD, Kotler DL, Kastenberg DM, Kistler CA. The gut microbiome and colorectal cancer: a review of bacterial pathogenesis. J Gastrointest Oncol. 2018;9(4):769–77.Google Scholar
  12. 12.
    Song M, Chan AT. Diet, gut microbiota, and colorectal cancer prevention: a review of potential mechanisms and promising targets for future research. Curr Colorectal Cancer Rep. 2017;13(6):429–39.Google Scholar
  13. 13.
    Nimptsch K, Wu K. Is timing important? The role of diet and lifestyle during early life on colorectal neoplasia. Curr Colorectal Cancer Rep. 2018;14(1):1–11.Google Scholar
  14. 14.
    Alexander JL, Scott AJ, Pouncey AL, Marchesi J, Kinross J, Teare J. Colorectal carcinogenesis: an archetype of gut microbiota-host interaction. Ecancermedicalscience. 2018;12:865.Google Scholar
  15. 15.
    Hashemi Goradel N, Heidarzadeh S, Jahangiri S, Farhood B, Mortezaee K, Khanlarkhani N, et al. Fusobacterium nucleatum and colorectal cancer: a mechanistic overview. J Cell Physiol. 2019;234(3):2337–2344.Google Scholar
  16. 16.
    Gholizadeh P, Eslami H, Kafil HS. Carcinogenesis mechanisms of Fusobacterium nucleatum. Biomed Pharmacother. 2017;89:918–25.Google Scholar
  17. 17.
    Park CH, Eun CS, Han DS. Intestinal microbiota, chronic inflammation, and colorectal cancer. Intest Res. 2018;16(3):338–45.Google Scholar
  18. 18.
    Niederreiter L, Adolph TE, Tilg H. Food, microbiome and colorectal cancer. Dig Liver Dis. 2018;50(7):647–52.Google Scholar
  19. 19.
    Sobhani I, Amiot A, Le Baleur Y, Levy M, Auriault ML, Van Nhieu JT, et al. Microbial dysbiosis and colon carcinogenesis: could colon cancer be considered a bacteria-related disease? Ther Adv Gastroenterol. 2013;6(3):215–29.Google Scholar
  20. 20.
    Kapatral V, Anderson I, Ivanova N, Reznik G, Los T, Lykidis A, et al. Genome sequence and analysis of the oral bacterium Fusobacterium nucleatum strain ATCC 25586. J Bacteriol. 2002;184(7):2005–18.Google Scholar
  21. 21.
    Brennan CA, Garrett WS. Fusobacterium nucleatum - symbiont, opportunist and oncobacterium. Nat Rev Microbiol. 2019;17(3):156–66.Google Scholar
  22. 22.
    Flanagan L, Schmid J, Ebert M, Soucek P, Kunicka T, Liska V, et al. Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur J Clin Microbiol Infect Dis. 2014;33(8):1381–90.Google Scholar
  23. 23.
    Moore WE, Holdeman LV, Smibert RM, Cato EP, Burmeister JA, Palcanis KG, et al. Bacteriology of experimental gingivitis in children. Infect Immun. 1984;46(1):1–6.Google Scholar
  24. 24.
    Zhang S, Cai S, Ma Y. Association between Fusobacterium nucleatum and colorectal cancer: progress and future directions. J Cancer. 2018;9(9):1652–9.Google Scholar
  25. 25.
    Ding T, Schloss PD. Dynamics and associations of microbial community types across the human body. Nature. 2014;509(7500):357–60.Google Scholar
  26. 26.
    Flynn KJ, Baxter NT, Schloss PD. Metabolic and community synergy of oral bacteria in colorectal cancer. mSphere. 2016;1(3).
  27. 27.
    •• Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X, Cai D, et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science. 2017;358(6369):1443–8 The authors show that treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These findings suggest further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer. Google Scholar
  28. 28.
    •• Hamada T, Zhang X, Mima K, Bullman S, Sukawa Y, Nowak JA, et al. Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status. Cancer Immunol Res. 2018;6(11):1327–36 The presence of Fusobacterium nucleatum in CRC tissue has been associated with microsatellite instability (MSI), lower-level T-cell infiltrates, and poor clinical outcomes. The association of Fusobacterium nucleatum with immune response to CRC differs by tumor MSI status, suggesting that Fusobacterium nucleatum and MSI status interact to affect antitumor immune reactions. Google Scholar
  29. 29.
    Hale VL, Jeraldo P, Chen J, Mundy M, Yao J, Priya S, et al. Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers. Genome Med. 2018;10(1):78.Google Scholar
  30. 30.
    Lee DW, Han SW, Kang JK, Bae JM, Kim HP, Won JK, et al. Association between Fusobacterium nucleatum, pathway mutation, and patient prognosis in colorectal cancer. Ann Surg Oncol. 2018;25(11):3389–3395.Google Scholar
  31. 31.
    Rubinstein MR, Wang X, Liu W, Hao Y, Cai G, Han YW. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013;14(2):195–206.Google Scholar
  32. 32.
    Han YW. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol. 2015;23:141–7.Google Scholar
  33. 33.
    Das V, Bhattacharya S, Chikkaputtaiah C, Hazra S, Pal M. The basics of epithelial-mesenchymal transition (EMT): a study from a structure, dynamics, and functional perspective. J Cell Physiol. 2019;234:14535–55.Google Scholar
  34. 34.
    Ma CT, Luo HS, Gao F, Tang QC, Chen W. Fusobacterium nucleatum promotes the progression of colorectal cancer by interacting with E-cadherin. Oncol Lett. 2018;16(2):2606–12.Google Scholar
  35. 35.
    Castellarin M, Warren RL, Freeman JD, Dreolini L, Krzywinski M, Strauss J, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22(2):299–306.Google Scholar
  36. 36.
    Yan X, Liu L, Li H, Qin H, Sun Z. Clinical significance of Fusobacterium nucleatum, epithelial-mesenchymal transition, and cancer stem cell markers in stage III/IV colorectal cancer patients. OncoTargets Ther. 2017;10:5031–46.Google Scholar
  37. 37.
    Yamaoka Y, Suehiro Y, Hashimoto S, Hoshida T, Fujimoto M, Watanabe M, et al. Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population. J Gastroenterol. 2018;53(4):517–24.Google Scholar
  38. 38.
    Ito M, Kanno S, Nosho K, Sukawa Y, Mitsuhashi K, Kurihara H, et al. Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway. Int J Cancer. 2015;137(6):1258–68.Google Scholar
  39. 39.
    Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K, Kurihara H, et al. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J Gastroenterol. 2016;22(2):557–66.Google Scholar
  40. 40.
    Grizzi F, Basso G, Borroni EM, Cavalleri T, Bianchi P, Stifter S, et al. Evolving notions on immune response in colorectal cancer and their implications for biomarker development. Inflamm Res. 2018;67(5):375–89.Google Scholar
  41. 41.
    Porta C, Ippolito A, Consonni FM, Carraro L, Celesti G, Correale C, et al. Protumor steering of cancer inflammation by p50 NF-kappaB enhances colorectal cancer progression. Cancer Immunol Res. 2018;6(5):578–93.Google Scholar
  42. 42.
    Di Caro G, Marchesi F, Laghi L, Grizzi F. Immune cells: plastic players along colorectal cancer progression. J Cell Mol Med. 2013;17(9):1088–95.Google Scholar
  43. 43.
    Malesci A, Bianchi P, Celesti G, Basso G, Marchesi F, Grizzi F, et al. Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer. Oncoimmunology. 2017;6(12):e1342918.Google Scholar
  44. 44.
    Galdiero MR, Bianchi P, Grizzi F, Di Caro G, Basso G, Ponzetta A, et al. Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer. Int J Cancer. 2016;139(2):446–56.Google Scholar
  45. 45.
    Wang HF, Li LF, Guo SH, Zeng QY, Ning F, Liu WL, et al. Evaluation of antibody level against Fusobacterium nucleatum in the serological diagnosis of colorectal cancer. Sci Rep. 2016;6:33440.Google Scholar
  46. 46.
    Xue Y, Xiao H, Guo S, Xu B, Liao Y, Wu Y, et al. Indoleamine 2,3-dioxygenase expression regulates the survival and proliferation of Fusobacterium nucleatum in THP-1-derived macrophages. Cell Death Dis. 2018;9(3):355.Google Scholar
  47. 47.
    Halstead SB, Mahalingam S, Marovich MA, Ubol S, Mosser DM. Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes. Lancet Infect Dis. 2010;10(10):712–22.Google Scholar
  48. 48.
    Chen T, Li Q, Wu J, Wu Y, Peng W, Li H, et al. Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism. Cancer Immunol Immunother. 2018;67(10):1635–1646.Google Scholar
  49. 49.
    Park HE, Kim JH, Cho NY, Lee HS, Kang GH. Intratumoral Fusobacterium nucleatum abundance correlates with macrophage infiltration and CDKN2A methylation in microsatellite-unstable colorectal carcinoma. Virchows Arch. 2017;471(3):329–36.Google Scholar
  50. 50.
    Guevarra LA Jr, Afable ACF, Belza PJO, Dy KJS, Lee SJQ, Sy-Ortin TT, et al. Immunogenicity of a Fap2 peptide mimotope of Fusobacterium nucleatum and its potential use in the diagnosis of colorectal cancer. Infect Agent Cancer. 2018;13:11.Google Scholar
  51. 51.
    Solomon BL, Garrido-Laguna I. TIGIT: a novel immunotherapy target moving from bench to bedside. Cancer Immunol Immunother. 2018;67(11):1659–1667.Google Scholar
  52. 52.
    •• Pages F, Mlecnik B, Marliot F, Bindea G, Ou FS, Bifulco C, et al. International validation of the consensus immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet. 2018;391(10135):2128–39 An international consortium of 14 centers in 13 countries assessed the prognostic value of total tumor-infiltrating T-cell counts and cytotoxic tumor-infiltrating T-cell counts with the consensus immunoscore assay in patients with stage I-III colon cancer. The immunoscore provides a reliable estimate of the risk of recurrence in patients with colon cancer. These results support the implementation of the consensus immunoscore as a new component of a TNM-immune classification of cancer. Google Scholar
  53. 53.
    Shunyakov L, Ryan CK, Sahasrabudhe DM, Khorana AA. The influence of host response on colorectal cancer prognosis. Clin Colorectal Cancer. 2004;4(1):38–45.Google Scholar
  54. 54.
    Titu LV, Monson JR, Greenman J. The role of CD8(+) T cells in immune responses to colorectal cancer. Cancer Immunol Immunother. 2002;51(5):235–47.Google Scholar
  55. 55.
    Dalerba P, Maccalli C, Casati C, Castelli C, Parmiani G. Immunology and immunotherapy of colorectal cancer. Crit Rev Oncol Hematol. 2003;46(1):33–57.Google Scholar
  56. 56.
    Scurr M, Gallimore A, Godkin A. T cell subsets and colorectal cancer: discerning the good from the bad. Cell Immunol. 2012;279(1):21–4.Google Scholar
  57. 57.
    Whiteside TL. What are regulatory T cells (Treg) regulating in cancer and why? Semin Cancer Biol. 2012;22(4):327–34.Google Scholar
  58. 58.
    Whiteside TL, Schuler P, Schilling B. Induced and natural regulatory T cells in human cancer. Expert Opin Biol Ther. 2012;12(10):1383–97.Google Scholar
  59. 59.
    Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6(4):295–307.Google Scholar
  60. 60.
    Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299(5609):1057–61.Google Scholar
  61. 61.
    Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306.Google Scholar
  62. 62.
    Alexander J, Watanabe T, Wu TT, Rashid A, Li S, Hamilton SR. Histopathological identification of colon cancer with microsatellite instability. Am J Pathol. 2001;158(2):527–35.Google Scholar
  63. 63.
    Graham DM, Appelman HD. Crohn’s-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator. Mod Pathol. 1990;3(3):332–5.Google Scholar
  64. 64.
    Aloisi F, Pujol-Borrell R. Lymphoid neogenesis in chronic inflammatory diseases. Nat Rev Immunol. 2006;6(3):205–17.Google Scholar
  65. 65.
    Carragher DM, Rangel-Moreno J, Randall TD. Ectopic lymphoid tissues and local immunity. Semin Immunol. 2008;20(1):26–42.Google Scholar
  66. 66.
    Bergomas F, Grizzi F, Doni A, Pesce S, Laghi L, Allavena P, et al. Tertiary intratumor lymphoid tissue in colo-rectal cancer. Cancers. 2011;4(1):1–10.Google Scholar
  67. 67.
    Mima K, Sukawa Y, Nishihara R, Qian ZR, Yamauchi M, Inamura K, et al. Fusobacterium nucleatum and T cells in colorectal carcinoma. JAMA Oncol. 2015;1(5):653–61.Google Scholar
  68. 68.
    Chen T, Li Q, Zhang X, Long R, Wu Y, Wu J, et al. TOX expression decreases with progression of colorectal cancers and is associated with CD4 T-cell density and Fusobacterium nucleatum infection. Hum Pathol. 2018;79:93–101.Google Scholar
  69. 69.
    Han YW, Shi W, Huang GT, Kinder Haake S, Park NH, Kuramitsu H, et al. Interactions between periodontal bacteria and human oral epithelial cells: Fusobacterium nucleatum adheres to and invades epithelial cells. Infect Immun. 2000;68(6):3140–6.Google Scholar
  70. 70.
    Jewett A, Hume WR, Le H, Huynh TN, Han YW, Cheng G, et al. Induction of apoptotic cell death in peripheral blood mononuclear and polymorphonuclear cells by an oral bacterium, Fusobacterium nucleatum. Infect Immun. 2000;68(4):1893–8.Google Scholar
  71. 71.
    Comerford I, Bunting M, Fenix K, Haylock-Jacobs S, Litchfield W, Harata-Lee Y, et al. An immune paradox: how can the same chemokine axis regulate both immune tolerance and activation?: CCR6/CCL20: a chemokine axis balancing immunological tolerance and inflammation in autoimmune disease. Bioessays. 2010;32(12):1067–76.Google Scholar
  72. 72.
    Liu J, Zhang N, Li Q, Zhang W, Ke F, Leng Q, et al. Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLoS One. 2011;6(4):e19495.Google Scholar
  73. 73.
    Gupte RS, Rawat DK, Chettimada S, Cioffi DL, Wolin MS, Gerthoffer WT, et al. Activation of glucose-6-phosphate dehydrogenase promotes acute hypoxic pulmonary artery contraction. J Biol Chem. 2010;285(25):19561–71.Google Scholar
  74. 74.
    Yamamura K, Baba Y, Nakagawa S, Mima K, Miyake K, Nakamura K, et al. Human microbiome Fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res. 2016;22(22):5574–81.Google Scholar
  75. 75.
    Wang B, Shi L, Sun X, Wang L, Wang X, Chen C. Production of CCL20 from lung cancer cells induces the cell migration and proliferation through PI3K pathway. J Cell Mol Med. 2016;20(5):920–9.Google Scholar
  76. 76.
    Cook KW, Letley DP, Ingram RJ, Staples E, Skjoldmose H, Atherton JC, et al. CCL20/CCR6-mediated migration of regulatory T cells to the helicobacter pylori-infected human gastric mucosa. Gut. 2014;63(10):1550–9.Google Scholar
  77. 77.
    Chen KJ, Lin SZ, Zhou L, Xie HY, Zhou WH, Taki-Eldin A, et al. Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis. PLoS One. 2011;6(9):e24671.Google Scholar
  78. 78.
    Liu JY, Li F, Wang LP, Chen XF, Wang D, Cao L, et al. CTL- vs Treg lymphocyte-attracting chemokines, CCL4 and CCL20, are strong reciprocal predictive markers for survival of patients with oesophageal squamous cell carcinoma. Br J Cancer. 2015;113(5):747–55.Google Scholar
  79. 79.
    Ye X, Wang R, Bhattacharya R, Boulbes DR, Fan F, Xia L, et al. Fusobacterium nucleatum subspecies animalis influences proinflammatory cytokine expression and monocyte activation in human colorectal tumors. Cancer Prev Res. 2017;10(7):398–409.Google Scholar
  80. 80.
    Rubie C, Oliveira V, Kempf K, Wagner M, Tilton B, Rau B, et al. Involvement of chemokine receptor CCR6 in colorectal cancer metastasis. Tumour Biol. 2006;27(3):166–74.Google Scholar
  81. 81.
    Zhang G, Chen R, Rudney JD. Streptococcus cristatus modulates the Fusobacterium nucleatum-induced epithelial interleukin-8 response through the nuclear factor-kappa B pathway. J Periodontal Res. 2011;46(5):558–67.Google Scholar
  82. 82.
    Huang GT, Zhang HB, Dang HN, Haake SK. Differential regulation of cytokine genes in gingival epithelial cells challenged by Fusobacterium nucleatum and Porphyromonas gingivalis. Microb Pathog. 2004;37(6):303–12.Google Scholar
  83. 83.
    Shin J, Ji S, Choi Y. Ability of oral bacteria to induce tissue-destructive molecules from human neutrophils. Oral Dis. 2008;14(4):327–34.Google Scholar
  84. 84.
    Sheikhi M, Gustafsson A, Jarstrand C. Cytokine, elastase and oxygen radical release by Fusobacterium nucleatum-activated leukocytes: a possible pathogenic factor in periodontitis. J Clin Periodontol. 2000;27(10):758–62.Google Scholar
  85. 85.
    Tang B, Wang K, Jia YP, Zhu P, Fang Y, Zhang ZJ, et al. Fusobacterium nucleatum-induced impairment of autophagic flux enhances the expression of proinflammatory cytokines via ROS in Caco-2 cells. PLoS One. 2016;11(11):e0165701.Google Scholar
  86. 86.
    Farhana L, Antaki F, Murshed F, Mahmud H, Judd SL, Nangia-Makker P, et al. Gut microbiome profiling and colorectal cancer in African Americans and Caucasian Americans. World J Gastrointest Pathophysiol. 2018;9(2):47–58.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Elena Monica Borroni
    • 1
    • 2
  • Dorina Qehajaj
    • 3
  • Floriana Maria Farina
    • 1
    • 2
  • Daniel Yiu
    • 4
  • Robert S. Bresalier
    • 5
  • Maurizio Chiriva-Internati
    • 5
    • 6
    • 7
  • Leonardo Mirandola
    • 7
  • Sanja Štifter
    • 8
  • Luigi Laghi
    • 9
    • 10
  • Fabio Grizzi
    • 3
    • 11
    Email author
  1. 1.Department of Biotechnology and Translational MedicineUniversity of MilanMilanItaly
  2. 2.Department of Leukocyte BiologyHumanitas Clinical and Research CenterMilanItaly
  3. 3.Department of Immunology and InflammationHumanitas Clinical and Research CenterMilanItaly
  4. 4.Department of General SurgeryFrimley Health NHS Foundation TrustSloughUK
  5. 5.Department of Gastroenterology, Hepatology and Nutrition, Division of Internal MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  6. 6.Department of Lymphoma and MyelomaThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Kiromic Inc.HoustonUSA
  8. 8.Department of PathologyClinical Hospital Center RijekaRijekaCroatia
  9. 9.Department of GastroenterologyHumanitas Clinical and Research CenterMilanItaly
  10. 10.Hereditary Cancer Genetics ClinicHumanitas Clinical and Research CenterMilanItaly
  11. 11.Histology CoreHumanitas Clinical and Research CenterMilanItaly

Personalised recommendations