The Role of the Intestinal Microbiome in the Immunotherapy of Colon Cancer
https://doi.org/10.18027/2224-5057-2019-9-2-5-11
Abstract
Genetic factors, immune dysfunction, chronic inflammation, and dysbiosis of the intestinal microbiome (IM) are believed to participate in the pathogenesis of colorectal cancer (CRC). The positive role of IM regulation in the treatment of inflammatory bowel disorders is determined by a reduction in the growth of pathogenic bacteria and an increase in the production of anti-inflammatory factors. Currently, the available data suggests that the IM dysregulates the immune response against the tumor in its microenvironment, thus either slowing down or accelerating the efficacy of antitumor therapy. Clinical studies have reported benefits of CRC therapy selected based on IM in improving immune intestinal homeostasis, epithelial barrier functions, and quality of life. Moreover, the specific IM signature may modulate the sensitivity to chemoand/ or radiotherapy, as well as the prognosis in patients with colorectal cancer. In this article, we presented the general challenges of the CRC therapy based on IM data in combination with immunotherapy, and described the future prospects of this approach.
About the Authors
G. G. Khakimova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation
Competing Interests: no conflict of interest
Russian Federation
Gulnoz G. Khakimova, postgraduate student, Department of Chemotherapy and Combined Treatment of Malignant Tumors.
Moscow
Competing Interests: no conflict of interest
A. A. Tryakin
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation
Competing Interests: no conflict of interest
Russian Federation
Alexey A. Tryakin - MD, PhD, DSc, Senior Researcher, Department of Clinical Pharmacology and Chemotherapy.
Moscow
Competing Interests: no conflict of interest
T. N. Zabotina
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation
Competing Interests: no conflict of interest
Russian Federation
Tatyana N. Zabotina - MD, DSC Biol, Head of Centralized Clinical and Laboratory Department.
Moscow
Competing Interests: no conflict of interest
A. S. Tsukanov
State Scientific Center of Coloproctology
Russian Federation
Competing Interests: no conflict of interest
Russian Federation
Alexey S. Tsukanov - MD, PhD, DSc, Head of Laboratory Genetics Department.
Moscow
Competing Interests: no conflict of interest
V. A. Aliev
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation
Competing Interests: no conflict of interest
Russian Federation
Vyacheslav A. Aliev - MD, PhD, DSc, Senior Researcher, Department of Coloproctology.
Moscow
Competing Interests: no conflict of interest
S. L. Gutorov
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation
Competing Interests: no conflict of interest
Russian Federation
Sergey L. Gutorov - MD, PhD, DSc, Leading Researcher, Department of Chemotherapy and Combined Treatment of Malignant Tumors.
Moscow
Competing Interests: no conflict of interest
References
1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, JemalA. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65 (2):87-108.
2. Fearon ER. Molecular genetics of colorectal cancer. Ann Rev Pathol. 2011;6 (1):479-507.
3. Jafri SH, Mills G. Lifestyle modification in colorectal cancer patients: an integrative oncology approach. Future Oncol. 2013;9 (2):207-218.
4. Okugawa Y, Grady WM, Goel A. Epigenetic alterations in colorectal cancer: emerging biomarkers. Gastroenterology. 2015;149 (5):1204-1225.
5. Lasry A, Zinger A, Ben-Neriah Y. Inflammatory networks underlying colorectal cancer. Nat Immunol. 2016;17 (3):230-240.
6. O'Keefe SJ. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016;13 (12):691-706.
7. Jess T, Simonsen J, Jcrgensen KT, Pedersen BV, Nielsen NM, Frisch M. Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology. 2012;143 (2):375-381.
8. Jess T, Horvath-Puho E, Fallingborg J, Rasmussen HH, Jacobsen BA. Cancer risk in inflammatory bowel disease according to patient phenotype and treatment: a Danish population-based cohort study. Am J Gastroenterol. 2013;108 (12):1869-1876.
9. Johnson CM, Wei C, Ensor JE, et al. Meta-analyses of colorectal cancer risk factors. Cancer Causes Control. 2013;24 (6):1207-1222.
10. Farraye FA, Odze RD, Eaden J, Itzkowitz SH. AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology. 2010;138 (2):738-745.
11. Lasry A, Zinger A, Ben-Neriah Y. Inflammatory networks underlying colorectal cancer. Nat Immunol. 2016;17 (3):230-240.
12. Johnson CM, Wei C, Ensor JE, et al. Meta-analyses of colorectal cancer risk factors. Cancer Causes Control. 2013;24 (6):1207-1222.
13. Kostic AD, Chun E, Meyerson M, Garrett WS. Microbes and inflammation in colorectal cancer. Cancer Immunol Res. 2013;1 (3):150-157.
14. Bruner SD, Jobin C. Intestinal microbiota in inflammatory bowel disease and carcinogenesis: implication for therapeutics. Clin Pharmacol Ther. 2016;99 (6):585-587.
15. Ijssennagger N, van der Meer R, van Mil SWC. Sulfide as a mucus barrier-breaker in inflammatory bowel disease? Trends Mol Med. 2016; 22 (3):190-199.
16. Uronis JM, Muhlbauer M, Herfarth HH, Rubinas TC, Jones GS, Jobin C. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PLoS One. 2009;4 (6):e6026.
17. Li Y, Kundu P, Seow SW, et al. Gut microbiota accelerate tumor growth via c-jun and STAT3 phosphorylation in APC Min/ + mice. Carcinogenesis. 2012;33 (6):1231—1238.
18. Васильев А.Н. Трансплантация фекальной микробиоты: возможные терапевтические подходы и вопросы правового регулирования / А.Н. Васильев, Д.В. Горячев, Е.В. Гавришина и др. // Биопрепараты. Рецензируемый научно-практический журнал. 2015. No 2 (54) С. 15-23.
19. Yu J, Feng Q, Wong SH, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017;66 (1):70-78.
20. Crawford PA, Gordon JI. From the cover: microbial regulation of intestinal radiosensitivity. Proc Natl Acad Sci. 2005;102 (37): 13254-13259.
21. Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017; 170 (3):548-563.
22. Vetizou M, Pitt JM, Daillere R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015; 350 (6264):1079-1084.
23. Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1 based immunotherapy against epithelial tumors. Science. 2018;359 (6371):91-97.
24. Ahmed S, Johnson K, Ahmed O, Iqbal N. Advances in the management of colorectal cancer: from biology to treatment. Int J Colorectal Dis. 2014;29 (9):1031-1042.
25. Field K, Lipton L. Metastatic colorectal cancer-past, progress and future. World J Gastroenterol. 2007;13 (28):3806-3815.
26. Dejea CM, Wick EC, Hechenbleikner EM, et al. Microbiota organization is a distinct feature of proximal colorectal cancers. Proc Natl Acad Sci. 2014;111 (51):18321-18326.
27. Li S, Konstantinov SR, Smits R, Peppelenbosch MP. Bacterial biofilms in colorectal cancer initiation and progression. Trends Mol Med. 2017; 23 (1):18-30.
28. Sicard J-F, Le Bihan G, Vogeleer P, Jacques M, Harel J. Interactions of intestinal bacteria with components of the intestinal mucus. Front Cell Infect Microbiol. 2017 ;7:387.
29. Yu J, Feng Q, Wong SH, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017;66 (1):70-78.
30. Nakatsu G, Li X, Zhou H, et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun. 2015;6 (1):8727.
31. Huipeng W, Lifeng G, Chuang G, Jiaying Z, Yuankun C. The differences in colonic mucosal microbiota between normal individual and colon cancer patients by polymerase chain reaction-denaturing gradient gel electrophoresis. J Clin Gastroenterol. 2014;48 (2):138-144.
32. Warren RL, Freeman DJ, Pleasance S, et al. Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome. 2013;1 (1):16.
33. Wu N, Yang X, Zhang R, et al. Dysbiosis signature of fecal microbiota in colorectal cancer patients. Microb Ecol. 2013;66 (2):462-470.
34. Kahouli I, Tomaro-Duchesneau C, Prakash S. Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives. J Med Microbiol. 2013;62 (Pt_8):1107-1123.
35. Ito M, Kanno S, Nosho K, et al. Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway. Int J Cancer. 2015;137 (6):1258-1268.
36. Park CH, Han DS, Oh Y-H, Lee A-Reum, Lee Y-Ra, Eun CS. Role of Fusobacteria in the serrated pathway of colorectal carcinogenesis. Sci Rep. 2016;6 (1):25271.
37. Ye X, Wang R, Bhattacharya R, 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.
38. 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):557-566.
39. de Vries NL, Swets M, Vahrmeijer AL, Hokland M, Kuppen PJ. The immunogenicity of colorectal cancer in relation to tumor development and treatment. Int J Mol Sci. 2016;17 (7):E1030.
40. Nishino M, Ramaiya NH, Hatabu H, Hodi FS. Monitoring immunecheckpoint blockade: response evaluation and biomarker development. Nat Rev Clin Oncol. 2017;14 (11):655—668.
41. Stewart CA, Metheny H, Iida N, et al. Interferon-dependent IL-10 production by Tregs limits tumor Th17 inflammation. J Clin Invest. 2013;123 (11):4859-4874.
42. Pang Y, Gara SK, Achyut BR, et al. TGF-P signaling in myeloid cells is required for tumor metastasis. Cancer Discov. 2013;3 (8):936-951.
43. Qian X, Chen H, Wu X, Hu L, Huang Q, Jin Y. Interleukin-17 acts as double-edged sword in anti-tumor immunity and tumorigenesis. Cytokine. 2017;89:34-44.
44. Pitt JM, Vetizou M, Waldschmitt N, et al. Fine-tuning cancer immunotherapy: optimizing the gut microbiome. Cancer Res. 2016; 76 (16):4602-4607.
45. West NR, Powrie F. Immunotherapy not working? Check your microbiota. Cancer Cell. 2015;28 (6):687-689.
46. Snyder A, Pamer E, Wolchok J. Immunotherapy. Could microbial therapy boost cancer immunotherapy? Science. 2015;350 (6264):1031-1032.
47. Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res. 2017;27 (1):109-118.
48. Geis AL, Fan H, Wu X, et al. Regulatory T-cell response to entero-toxigenic Bacteroides fragilis colonization triggers IL17-dependent colon carcinogenesis. Cancer Discov. 2015;5 (10):1098-1109.
49. Viaud S, Saccheri F, Mignot G, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342 (6161):971-976.
50. Baecher-Allan C, Viglietta V, Hafler DA. Human CD4+CD25+ regulatory T cells. Semin Immunol. 2004;16 (2):89-98.
51. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 2002; 3 (7):611-618.
52. Vetizou M, Pitt JM, Daillere R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015; 350 (6264):1079-1084.
53. Dubin K, Callahan MK, Ren B, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun. 2016;7:10391.
54. Nishino M, Ramaiya NH, Hatabu H, Hodi FS. Monitoring immunecheckpoint blockade: response evaluation and biomarker development. Nat Rev Clin Oncol. 2017;14 (11):655-668.
55. Gopalakrishnan V, Spencer CN, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359 (6371):97-103.
56. Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350 (6264):1084-1089.
57. Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359 (6371):104-108.
58. Jin P, Wang K, Huang C, Nice EC. Mining the fecal proteome: from biomarkers to personalised medicine. Expert Rev Proteomics. 2017; 14 (5):445-459.
59. Ai L, Tian H, Chen Z, Chen H, Xu J, Fang JY. Systematic evaluation of supervised classifiers for fecal microbiota-based prediction of colorectal cancer. Oncotarget. 2017;8 (6):9546-9556.
60. Zhang MM, Cheng JQ, Xia L, et al. Monitoring intestinal microbiota profile: a promising method for the ultraearly detection of colorectal cancer. Med Hypotheses. 2011;76 (5):670-672.
61. Shah MS, Desantis TZ, Weinmaier T, et al. Leveraging sequencebased faecal microbial community survey data to identify a composite biomarker for colorectal cancer. Gut. 2018;67 (5):882-891.
62. Enq RR. How's your microbiota? Let's check your urine. Blood. 2015; 126 (14):1641-1642.
63. Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, et al. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut. 2018;67 (2):226-236.
64. Panteli JT, Forkus BA, van Dessel N, Forbes NS. Genetically modified bacteria as a tool to detect microscopic solid tumor masses with triggered release of a recombinant biomarker. Integr Biol. 2015;7 (4):423-434.
65. Gardlik R, Fruehauf JH. Bacterial vectors and delivery systems in cancer therapy. IDrugs. 010;13(10):701-706.
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For citations:
Khakimova G.G., Tryakin A.A., Zabotina T.N., Tsukanov A.S., Aliev V.A., Gutorov S.L. The Role of the Intestinal Microbiome in the Immunotherapy of Colon Cancer. Malignant tumours. 2019;9(2):5-11. (In Russ.) https://doi.org/10.18027/2224-5057-2019-9-2-5-11
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