Dynamic relationships among tumor, immune response, and microbiota

Takuya Tsunoda, Kazunori Shimada, Naoki Uchida, Shinichi Kobayashi, Yasutsuna Sasaki

Article ID: 79
Vol 3, Issue 1, 2019

VIEWS - 1043 (Abstract) 681 (PDF)

Abstract


Recently, the analysis of microbiota has been of interest not only for the clarification of the molecular mechanisms of disease etiology, but also the discovery of novel strategies for treatment. Following the development of "next-generation" sequencing, novel areas have been discovered in microbiota; however, in oncology, the relationships between microbiota and cancer have not been fully clarified. In recent literature, surprisingly, detection of gut microbiota in tumor issue itself has been reported. Microbiota might play an important role in carcinogenesis. However, this phenomenon is not well understood, and research in this area has just begun. In the past five years, a paradigm shift has occurred in cancer treatment due to immunotherapy. Immunotherapy has made cure possible even in advanced cancer patients with not only melanoma but also non-small cell lung cancer and others. In this review, we discuss the mechanisms of novel immunotherapies, checkpoint inhibitors, and the relationship between microbiota and immunotherapy. It is of significance to clarify this relationship because it may lead to the discovery of predictive markers for immunotherapy and promote clinical efficacy. Finally, we also mention our activities in the construction of a big database for information on immunotherapy and microbiota, which may lead to excellent possibilities of discovering novel strategies for more effective cancer treatments, and may accelerate the alteration of cancers to the classification of chronic nonfatal disease.

Keywords


gut microbiota; immunotherapy; check point inhibitors; cancer treatment; immunoresponse

Full Text:

PDF


References


1. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009; 9(5): 313–323. doi: 10.1038/nri2515.

2. Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006; 124(4): 837–848. doi: 10.1016/j.cell.2006.02.017.

3. Atarashi K, Honda K. Microbiota in autoimmunity and tolerance. Curr Opin Immunol 2011; 23(6): 761–768. doi: 10.1016/j.coi.2011.11.002.

4. Matamoros S, Gras-Leguen C, Le Vacon F, et al. Development of intestinal microbiota in infants and its impact on health. Trends Microbiol 2013; 21(4): 167–173. doi: 10.1016/j.tim.2012.12.001.

5. Zeng MY, Inohara N, Nuñez G. Mechanisms of inflammation-driven bacterial dysbiosis in the gut. Mucosal Immunol 2016; 10(1): 18–26. doi: 10.1038/mi.2016.75.

6. Lederberg J. Infectious history. Science 2000; 288(5464): 287–293. doi: 10.1126/science.288.5464.287.

7. Mackowiak PA. The normal microbial flora. N Engl J Med 1982; 307(2): 83–93. doi: 10.1056/NEJM198207083070203.

8. Lin L, Zhang J. Role of intestinal microbiota and metabolites on gut homeostasis and human diseases. BMC Immunology 2017; 18: 2. doi: 10.1186/s12865-016-0187-3.

9. Blaser MJ. The microbiome revolution. Clin Invest 2014; 124(10): 4162–4165. doi: 10.1172/JCI78366.

10. Blacher E, Levy M, Tatirovsky E, et al. Microbiome-modulated metabolites at the interface of host immunity. J Immunol 2017; 198(2): 572–580. doi: 10.4049/jimmunol.1601247.

11. Schroeder BO, Bäckhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med 2016; 22(10): 1079–1089. doi: 10.1038/nm.4185.

12. Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: Current status and the future ahead. Gastroenterology 2014; 146(6): 1489–1499. doi: 10.1053/j.gastro.2014.02.009.

13. Eck A, de Groot EFJ, de Meij TGJ, et al. Robust microbiota-based diagnostics for inflammatory bowel disease. J Clin Microbiol 2017; 55(6): 1720–1732. doi: 10.1128/JCM.00162-17.

14. Nagao-Kitamoto H, Kamada N. Host-microbial cross-talk in inflammatory bowel disease. Immune Netw 2017; 17(1): 1–12. doi: 10.4110/in.2017.17.1.1.

15. Reinisch W. Fecal microbiota transplantation in inflammatory bowel disease. Dig Dis 2017; 35(1–2): 123–126. doi: 10.1159/000449092.

16. Giongo A, Gano KA, Crabb DB, et al. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 2011; 5(1): 82–91. doi: 10.1038/ismej.2010.92.

17. Wang F, Zhang C, Zeng Q. Gut microbiota and immunopathogenesis of diabetes mellitus type 1 and 2. Front Biosci (Landmark Ed) 2016; 21: 900–906. doi: 10.2741/4427.

18. Barlow GM, Yu A, Mathur R. Role of the gut microbiome in obesity and diabetes mellitus. Nutr Clin Pract 2015; 30(6): 787–797. doi: 10.1177/0884533615609896.

19. Ochoa-Repáraz J, Mielcarz DW, Begum-Haque S, et al. Gut, bugs, and brain: Role of commensal bacteria in the control of central nervous system disease. Ann Neurol 2011; 69(2): 240–247. doi: 10.1002/ana.22344.

20. Lyte M. Microbial endocrinology and the microbiota-gut-brain axis. In: Lyte M, Cryan JF (editors). Microbial endocrinology: The microbiota-gut-brain axis in health and disease. New York, NY, USA: Springer; 2014. p. 3–25. doi: 10.1007/978-1-4939-0897-4_1.

21. Blanchard EB, Scharff L, Schwarz SP, et al. The role of anxiety and depression in the irritable bowel syndrome. Behav Res Ther 1990; 28(5): 401–405. doi: 10.1016/0005-7967(90)90159-G.

22. Erny D, de Angelis ALH, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 2015; 18(7): 965–977. doi: 10.1038/nn.4030.

23. Prinz M, Priller J. Microglia and brain macrophages in the molecular age: From origin to neuropsychiatric disease. Nat Rev Neurosci 2014; 15(5): 300–312. doi: 10.1038/nrn3722.

24. Schafer DP, Stevens B. Phagocytic glial cells: Sculpting synaptic circuits in the developing nervous system. Curr Opin Neurobiol 2013; 23(6): 1034–1040. doi: 10.1016/j.conb.2013.09.012.

25. Halken S, Høst A, Hansen LG, et al. Effect of an allergy prevention programme on incidence of atopic symptoms in infancy. A prospective study of 159 “high-risk” infants. Allergy 1992; 47(5): 545–553. doi: 10.1111/j.1398-9995.1992.tb00680.x.

26. Rottem M, Szyper-Kravitz M, Shoenfeld Y. Atopy and asthma in migrants. Int Arch Allergy Immunol 2005; 136(2): 198–204. doi: 10.1159/000083894.

27. van Nimwegen FA, Penders J, Stobberingh EE, et al. Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. J Allergy Clin Immunol 2011; 128(5): 948–955.e3. doi: 10.1016/j.jaci.2011.07.027.

28. Droste JH, Wieringa MH, Weyler JJ, et al. Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease? Clin Exp Allergy 2000; 30(11): 1547–1553. doi: 10.1046/j.1365-2222.2000.00939.x.

29. Hong SW, Kim KS, Surh CD. Beyond hygiene: Commensal microbiota and allergic diseases. Immune Netw 2017; 17(1): 48¬–59. doi: 10.4110/in.2017.17.1.48.

30. Lyte M. The role of microbial endocrinology in infectious disease. J Endocrinol 1993; 137(3): 343–345. doi: 10.1677/joe.0.1370343.

31. Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015; 350(6264): 1079–1084. doi: 10.1126/science.aad1329.

32. 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. doi: 10.1126/science.aac4255.

33. Gopalakrishnan V, Spencer C, Reuben A, et al. Response to anti-PD-1 based therapy in metastatic melanoma patients is associated with the diversity and composition of the gut microbiome. Proceedings: AACR Annual Meeting 2017; 77(13 Supp): 2672. doi: 10.1158/1538-7445.AM2017-2672.

34. Nishijima S, Suda W, Oshima K, et al. The gut microbiome of healthy Japanese and its microbial and functional uniqueness. DNA Res 2016; 23(2): 125–133. doi: 10.1093/dnares/dsw002.

35. Kim SW, Suda W, Kim S, et al. Robustness of gut microbiota of healthy adults in response to probiotic intervention revealed by high-throughput pyrosequencing, DNA Res 2013; 20(3): 241–253. doi: 10.1093/dnares/dst006.

36. Yang J, Tan Q, Fu Q, et al. Gastrointestinal microbiome and breast cancer: Correlations, mechanisms and potential clinical implications. Breast Cancer 2017; 24(2): 220–228. doi: 10.1007/s12282-016-0734-z.

37. Luu TH, Michel C, Bard J-M, et al. Intestinal proportion of Blautia sp. is associated with clinical stage and histoprognostic grade in patients with early-stage breast cancer. Nutr Cancer 2017; 69(2): 267¬–275. doi: 10.1080/01635581.2017.1263750.

38. Urbaniak C, Gloor GB, Brackstone M, et al. The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol 2016; 82(16): 5039¬–5048. doi: 10.1128/AEM.01235-16.

39. Urbaniak C, Cummins J, Brackstone M, et al. Microbiota of human breast tissue. Appl Environ Microbiol 2014; 80(10): 3007–3014. doi: 10.1128/AEM.00242-14.

40. Mehta RS, Nishihara R, Cao Y, et al. Association of dietary patterns with risk of colorectal cancer subtypes classified by Fusobacterium nucleatum in tumor tissue. JAMA Oncol 2017; 3(7): 921–927. doi: 10.1001/jamaoncol.2016.6374.

41. Mira-Pascual L, Cabrera-Rubio R, Ocon S, al. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol 2015; 50(2): 167–179. doi: 10.1007/s00535-014-0963-x.

42. Dos Reis SA, da Conceição LL, Siqueira NP, et al. Review of the mechanisms of probiotic actions in the prevention of colorectal cancer. Nutr Res 2017; 37: 1–19. doi: 10.1016/j.nutres.2016.11.009.

43. 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. doi: 10.3748/wjg.v22.i2.557.

44. Mima K, Sukawa Y, Nishihara R, et al. Fusobacterium nucleatum and T Cells in colorectal carcinoma. JAMA Oncol 2015; 1(5): 653–661. doi: 10.1001/jamaoncol.2015.1377.

45. Roy S, Trinchieri G. Microbiota: A key orchestrator of cancer therapy. Nat Rev Cancer 2017; 17(5): 271–285. doi: 10.1038/nrc.2017.13.

46. Alexander JL, Wilson ID, Teare J, et al. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol 2017; 14(6): 356–365. doi: 10.1038/nrgastro.2017.20.

47. Dzutsev A, Badger JH, Perez-Chanona E, et al. Microbes and cancer. Annu Rev Immunol 2017; 35: 199–228. doi: 10.1146/annurev-immunol-051116-052133.

48. Contreras AV, Cocom-Chan B, Hernandez-Montes G, et al. Host-microbiome interaction and cancer: Potential application in precision medicine. Front Physiol 2016; 7: 606. doi: 10.3389/fphys.2016.00606.

49. Erdman SE, Poutahidis T. Gut microbiota modulate host immune cells in cancer development and growth. Free Radic Biol Med 2016; 105: 28–34. doi: 10.1016/j.freeradbiomed.2016.11.013.

50. Lee CS, Thomas CM, Ng KE. An overview of the changing landscape of treatment for advanced melanoma. Pharmacotherapy 2017; 37(3): 319–333. doi: 10.1002/phar.1895.

51. Hoos A. Development of immuno-oncology drugs—from CTLA4 to PD1 to the next generations. Nat Rev Drug Discov 2016; 15(4): 235–247. doi: 10.1038/nrd.2015.35.

52. Buchbinder E, Hodi FS. Cytotoxic T lymphocyte antigen-4 and immune checkpoint blockade. J Clin Invest 2015; 125(9): 3377–3383. doi; 10.1172/JCI80012.

53. Schadendorf D, Hodi FS, Robert C, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 2015; 33(17): 1889–1894. doi: 10.1200/JCO.2014.56.2736.

54. Eroglua Z, Kim DW, Wang X, et al. Long term survival with CTLA-4 blockade using tremelimumab. Eur J Cancer 2015; 51(17): 2689–2697. doi: 10.1016/j.ejca.2015.08.012.

55. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: Analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17(7): 2105–2116. doi: 10.1200/JCO.1999.17.7.2105.

56. Guo L, Zhang H, Chen B. Nivolumab as programmed death-1 (PD-1) inhibitor for targeted immunotherapy in tumor. J Cancer 2017; 8(3): 410–416. doi: 10.7150/jca.17144.

57. Bersanelli M, Buti S. From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis. World J Clin Oncol 2017; 8(1): 37–53. doi: 10.5306/wjco.v8.i1.37.

58. Balar AV, Weber JS. PD-1 and PD-L1 antibodies in cancer: Current status and future directions. Cancer Immunol Immunother 2017; 66(5): 551–564. doi: 10.1007/s00262-017-1954-6.

59. Dempke WCM, Fenchel K, Uciechowski P, et al. Second- and third-generation drugs for immuno-oncology treatment—The more the better? Eur J Cancer 2017; 74: 55–72. doi: 10.1016/j.ejca.2017.01.001.

60. Ishida Y, Agata Y, Shibahara K, et al. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J 1992; 11(11): 3887–3895.

61. Smithy JW, Moore LM, Pelekanou V, et al. Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma. J Immunother Cancer 2017; 5: 25. doi: 10.1186/s40425-017-0229-2.

62. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2016; 387(10027): 1540–1550. doi: 10.1016/S0140-6736(15)01281-7.

63. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med 2016; 375(19): 1823–1833. doi: 10.1056/NEJMoa1606774.

64. Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515(7528): 568–571. doi: 10.1038/nature13954.

65. Spranger S, Sivan A, Corrales L, et al. Tumor and host factors controlling antitumor immunity and efficacy of cancer immunotherapy. Adv Immunol 2016; 130: 75–93. doi: 10.1016/bs.ai.2015.12.003.

66. Taur Y, Jenq RR, Perales MA, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 2014; 124(7): 1174–1182. doi: 10.1182/blood-2014-02-554725.

67. Tauchi Y, Tanaka H, Kumamoto K, et al. Tumor-associated macrophages induce capillary morphogenesis of lymphatic endothelial cells derived from human gastric cancer. Cancer Sci 2016; 107(8): 1101–1109. doi: 10.1111/cas.12977.

68. Okita Y, Tanaka H, Ohira M, et al. Role of tumor-infiltrating CD11b+ antigen-presenting cells in the progression of gastric cancer. J Surg Res 2014; 186(1): 192–200. doi: 10.1016/j.jss.2013.08.024.

69. Yoshii M, Tanaka H, Ohira M, et al. Expression of Forkhead box P3 in tumour cells causes immunoregulatory function of signet ring cell carcinoma of the stomach. Br J Cancer 2012; 106(10): 1668–1674. doi: 10.1038/bjc.2012.141.

70. Yoshii M, Tanaka H, Ohira M, et al. Association of MHC class I expression and lymph node metastasis of gastric carcinoma. Hepatogastroenterology 2013; 60(123): 611–615. doi: 10.5754/hge12433.

71. Tamura T, Ohira M, Tanaka H, et al. Programmed death-1 ligand-1 (PDL1) expression is associated with the prognosis of patients with stage II/III gastric cancer. Anticancer Res 2015; 35(10): 5369–5376.




DOI: https://doi.org/10.24294/ti.v3.i1.79

Refbacks

  • There are currently no refbacks.


Copyright (c) 2019 Takuya Tsunoda

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

This site is licensed under a Creative Commons Attribution 4.0 International License.