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The cancer microbiome - Nature Reviews Cancer

  • ️Wargo, Jennifer
  • ️Tue Jun 11 2019
  • Viewpoint
  • Published: 11 June 2019

Nature Reviews Cancer volume 19, pages 371–376 (2019)Cite this article

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Abstract

Collectively known as the microbiota, the commensal bacteria and other microorganisms that colonize the epithelial surfaces of our body have been shown to produce small molecules and metabolites that have both local and systemic effects on cancer onset, progression and therapy response. To date, most studies focusing on the microbiome have used traditional preclinical mouse models and identified correlative relationships between microbial species and cancer phenotypes. Now, the profound influence of the microbiota on the efficacy of cancer treatments, such as immunotherapies, has begun to be extensively characterized in humans. Paramount to the development of microbiota-based therapeutics, the next challenge in microbiome research will be to identify individual microbial species that causally affect cancer phenotypes and unravel the underlying mechanisms. In this Viewpoint article, we asked four scientists working on the cancer microbiome for their opinions on the current state of the field, where the research is heading and how we can advance our understanding to rationally design microbial-based therapeutics to transform treatment strategies for patients with cancer.

The contributors

Eran Elinav is a professor in the Immunology Department, Weizmann Institute of Science, Israel, and the Director of the Cancer-Microbiome Division, Deutsches Krebsforschungszentrum (DKFZ), Germany. His research focuses on deciphering the molecular basis of host–microbiome interactions and their effects on health and disease, with a goal of personalizing medicine and nutrition.

Wendy S. Garrett is a professor of immunology and infectious diseases at Harvard and a medical oncologist in the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute. She is co-director of the Harvard Chan Center for the Microbiome in Public Health. Her laboratory seeks to carry out mechanistic microbiome studies focused on cancer, inflammatory bowel disease and immune and epithelial cell development and function.

Giorgio Trinchieri is a US National Institutes of Health (NIH) Distinguished Investigator and Director of the Cancer and Inflammation Program, Center for Cancer Research (CCR), National Cancer Institute (NCI), NIH. His research has focused for many years on the interplay between inflammation, innate resistance and adaptive immunity and on the role of pro-inflammatory cytokines and interferons in the regulation of haematopoiesis, innate resistance and immunity against infections and tumours. The present focus of his laboratory is on the role of inflammation, innate resistance, immunity and the commensal microbiota in carcinogenesis, cancer progression and prevention or therapy of cancer.

Jennifer Wargo is an Associate Professor of Surgical Oncology and Genomic Medicine at the University of Texas MD Anderson Cancer Center and is a co-leader of the Melanoma Moon Shot programme. Her primary interests are in response and resistance to targeted therapy for melanoma and other cancers, neoadjuvant strategies and the influence of the gut and tumour microbiome on immunity and antitumour immune responses.

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References

  1. Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018).

    Article  CAS  Google Scholar 

  2. Matson, V. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108 (2018).

    Article  CAS  Google Scholar 

  3. Pauli, C. et al. Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov. 7, 462–477 (2017).

    Article  Google Scholar 

  4. Sontheimer-Phelps, A., Hassell, B. A. & Ingber, D. E. Modelling cancer in microfluidic human organs-on-chips. Nat. Rev. Cancer 19, 65–81 (2019).

    Article  CAS  Google Scholar 

  5. Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).

    Article  CAS  Google Scholar 

  6. Bruynseels, K., Santoni de Sio, F. & van den Hoven, J. Digital twins in health care: ethical implications of an emerging engineering paradigm. Front. Genet. 9, 31 (2018).

    Article  Google Scholar 

  7. Drost, J. & Clevers, H. Organoids in cancer research. Nat. Rev. Cancer 18, 407–418 (2018).

    Article  CAS  Google Scholar 

  8. Fujii, M., Clevers, H. & Sato, T. Modeling human digestive diseases with CRISPR-Cas9-modified organoids. Gastroenterology 156, 562–576 (2019).

    Article  CAS  Google Scholar 

  9. Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565, 600–605 (2019).

    Article  CAS  Google Scholar 

  10. Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018).

    Article  CAS  Google Scholar 

  11. Wege, A. K., Melkus, M. W., Denton, P. W., Estes, J. D. & Garcia, J. V. Functional and phenotypic characterization of the humanized BLT mouse model. Curr. Top. Microbiol. Immunol. 324, 149–165 (2008).

    CAS  PubMed  Google Scholar 

  12. Young, G. R. et al. Resurrection of endogenous retroviruses in antibody-deficient mice. Nature 491, 774–778 (2012).

    Article  CAS  Google Scholar 

  13. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03341143 (2019).

  14. Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).

    Article  CAS  Google Scholar 

  15. Gharaibeh, R. Z. & Jobin, C. Microbiota and cancer immunotherapy: in search of microbial signals. Gut https://doi.org/10.1136/gutjnl-2018-317220 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Knight, R. et al. Best practices for analysing microbiomes. Nat. Rev. Microbiol. 16, 410–422 (2018).

    Article  CAS  Google Scholar 

  17. Blank, C. U., Haanen, J. B., Ribas, A. & Schumacher, T. N. The “cancer immunogram”. Science 352, 658–660 (2016).

    Article  CAS  Google Scholar 

  18. Cogdill, A. P., Andrews, M. C. & Wargo, J. A. Hallmarks of response to immune checkpoint blockade. Br. J. Cancer 117, 1–7 (2017).

    Article  Google Scholar 

  19. Zmora, N., Soffer, E. & Elinav, E. Transforming medicine with the microbiome. Sci. Transl Med. 11, eaaw1815 (2019).

    Article  Google Scholar 

  20. Shin, W. & Kim, H. J. Intestinal barrier dysfunction orchestrates the onset of inflammatory host-microbiome cross-talk in a human gut inflammation-on-a-chip. Proc. Natl Acad. Sci. USA 115, E10539–E10547 (2018).

    Article  CAS  Google Scholar 

  21. Rubinstein, M. R. et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 14, 195–206 (2013).

    Article  CAS  Google Scholar 

  22. Tahara, T. et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res. 74, 1311–1318 (2014).

    Article  CAS  Google Scholar 

  23. Bashiardes, S., Tuganbaev, T., Federici, S. & Elinav, E. The microbiome in anti-cancer therapy. Semin. Immunol. 32, 74–81 (2017).

    Article  CAS  Google Scholar 

  24. Geller, L. T. et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357, 1156–1160 (2017).

    Article  CAS  Google Scholar 

  25. Zhang, X. et al. Fecal fusobacterium nucleatum for the diagnosis of colorectal tumor: a systematic review and meta-analysis. Cancer Med. 8, 480–491 (2019).

    Article  Google Scholar 

  26. Forbes, N. S. et al. White paper on microbial anti-cancer therapy and prevention. J. Immunother. Cancer 6, 78 (2018).

    Article  Google Scholar 

  27. Iida, N. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342, 967–970 (2013).

    Article  CAS  Google Scholar 

  28. Viaud, S. et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342, 971–976 (2013).

    Article  CAS  Google Scholar 

  29. He, Y. et al. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat. Med. 24, 1532–1535 (2018).

    Article  CAS  Google Scholar 

  30. Vedanta Biosciences. Bristol-Myers Squibb and Vedanta Biosciences announce a new clinical collaboration to evaluate OPDIVO® (nivolumab) and VE800 in patients with advanced or metastatic cancers. Vedanta Biosciences https://www.vedantabio.com/news-media/press-releases/detail/2492 (2018).

  31. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03595683 (2018).

  32. Frankel, A. E. et al. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia 19, 848–855 (2017).

    Article  CAS  Google Scholar 

  33. Chaput, N. et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann. Oncol. 28, 1368–1379 (2017).

    Article  CAS  Google Scholar 

  34. Wang, Y. et al. Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. Nat. Med. 24, 1804–1808 (2018).

    Article  CAS  Google Scholar 

  35. McQuade, J. L., Daniel, C. R., Helmink, B. A. & Wargo, J. A. Modulating the microbiome to improve therapeutic response in cancer. Lancet Oncol. 20, e77–e91 (2019).

    Article  Google Scholar 

  36. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03353402 (2019).

  37. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03817125 (2019).

  38. Byrd, A. L., Belkaid, Y. & Segre, J. A. The human skin microbiome. Nat. Rev. Microbiol. 16, 143–155 (2018).

    Article  CAS  Google Scholar 

  39. Sethi, V. et al. Gut microbiota promotes tumor growth in mice by modulating immune response. Gastroenterology 155, 33–37 (2018).

    Article  CAS  Google Scholar 

  40. van der Velden, W. J. et al. Role of the mycobiome in human acute graft-versus-host disease. Biol. Blood Marrow Transplant. 19, 329–332 (2013).

    Article  Google Scholar 

  41. Mukherjee, P. K. et al. Bacteriome and mycobiome associations in oral tongue cancer. Oncotarget 8, 97273–97289 (2017).

    PubMed  PubMed Central  Google Scholar 

  42. Coker, O. O. et al. Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer. Gut 68, 654–662 (2018).

    Article  Google Scholar 

  43. Brindley, P. J., Costa, J. & Sripa, B. Why does infection with some helminths cause cancer? Trends Cancer 1, 174–182 (2015).

    Google Scholar 

  44. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological agents Volume 100 B. A review of human carcinogens. IARC Monogr. Eval. Carcinog. Risks Hum. 100, 1–441 (2012).

    PubMed Central  Google Scholar 

  45. Zhu, F. et al. Autoreactive T cells and chronic fungal infection drive esophageal carcinogenesis. Cell Host Microbe 21, 478–493 (2017).

    Article  CAS  Google Scholar 

  46. Draper, L. A. et al. Long-term colonisation with donor bacteriophages following successful faecal microbial transplantation. Microbiome 6, 220 (2018).

    Article  CAS  Google Scholar 

  47. Ott, S. J. et al. Efficacy of sterile fecal filtrate transfer for treating patients with Clostridium difficile infection. Gastroenterology 152, 799–811 (2017).

    Article  Google Scholar 

Download references

Acknowledgements

E.E. thanks all the students, postdocs and employees at the Elinav laboratory at Weizmann Institute of Science and Deutsches Krebsforschungszentrum (DKFZ) for their continued partnership. E.E. is a senior fellow of the Canadian Institute of Advanced Research (CIFAR) and an international scholar of the Bill and Melinda Gates Foundation and Howard Hughes Medical Institute (HHMI). W.S.G. thanks members of her laboratory and collaborators for stimulating discussions as well as the US National Institutes of Health (NIH) National Cancer Institute (NCI) and Cancer Research UK for research support. J.W. thanks the patients who contributed to these studies, as well as the faculty, staff, students and postdoctoral fellows at the University of Texas MD Anderson Cancer Center who contributed to this work (which was supported by the Melanoma Moon Shot programme). J.W. also thanks worldwide collaborators for providing critical insight and opportunities to learn together. J.W. is a member investigator of the Parker Institute for Cancer Immunotherapy and is also an awardee of an Innovative Research Grant from Stand Up to Cancer–American Association for Cancer Research. J.W.’s research efforts are also supported by a Sabin Family Fellowship, the Melanoma Research Alliance and the NIH (1R011CA219896-01A1).

Author information

Authors and Affiliations

  1. Immunology Department, Weizmann Institute of Science, Rehovot, Israel

    Eran Elinav

  2. Cancer-Microbiome Division, Deutsches Krebsforschungszentrum (DKFZ), Neuenheimer Feld 280, Heidelberg, Germany

    Eran Elinav

  3. Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA

    Wendy S. Garrett

  4. Broad Institute of Harvard and MIT, Cambridge, MA, USA

    Wendy S. Garrett

  5. Department and Division of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    Wendy S. Garrett

  6. Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Giorgio Trinchieri

  7. Department of Surgical Oncology and Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jennifer Wargo

Authors

  1. Eran Elinav

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  2. Wendy S. Garrett

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  3. Giorgio Trinchieri

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  4. Jennifer Wargo

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Corresponding authors

Correspondence to Eran Elinav, Wendy S. Garrett, Giorgio Trinchieri or Jennifer Wargo.

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Competing interests

E.E. is a paid consultant at DayTwo and BiomX. E.E. states that none of the issues covered in this piece are related to, funded or endorsed by, shared or discussed with or licensed to these commercial entities. W.S.G. is a member of the scientific advisory boards for Evelo Biosciences, Kintai Therapeutics and Leap Therapeutics. G.T. declares no competing financial interests. J.W. is an advisory board member and consultant and adviser for AstraZeneca, Bristol-Myers Squibb, F. Hoffman–La Roche–Genentech, GlaxoSmithKline, Merck Sharp & Dohme, MicrobiomeDX, Biothera Pharmaceuticals and Novartis Pharmaceuticals Corporation, receives grant, clinical and research support from Bristol-Myers Squibb, F. Hoffman–La Roche–Genentech, GlaxoSmithKline and Novartis Pharmaceuticals Corporation, is a speakers bureau participant with Bristol-Myers Squibb, Dava Oncology, Gilead Sciences, Illumina, Imedex, MedImmune and Omniprex and receives other financial or material support from a US patent application (PCT/US17/53.717) submitted by the University of Texas MD Anderson Cancer Center that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome.

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Elinav, E., Garrett, W.S., Trinchieri, G. et al. The cancer microbiome. Nat Rev Cancer 19, 371–376 (2019). https://doi.org/10.1038/s41568-019-0155-3

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  • Accepted: 26 April 2019

  • Published: 11 June 2019

  • Issue Date: July 2019

  • DOI: https://doi.org/10.1038/s41568-019-0155-3

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