Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth (original) (raw)

Change history

The FACS image in Fig. 1e was corrected; scale bars in Figs 3b, e and f and 4a, b and f were amended.

References

  1. Vogelstein, B. & Kinzler, K. W. Cancer genes and the pathways they control. Nature Med. 10, 789–799 (2004)
    Article CAS Google Scholar
  2. Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759–767 (1990)
    Article CAS Google Scholar
  3. Wood, L. D. et al. The genomic landscapes of human breast and colorectal cancers. Science 318, 1108–1113 (2007)
    Article ADS CAS Google Scholar
  4. Reichling, T. et al. Transcriptional profiles of intestinal tumors in Apc(Min) mice are unique from those of embryonic intestine and identify novel gene targets dysregulated in human colorectal tumors. Cancer Res. 65, 166–176 (2005)
    CAS PubMed Google Scholar
  5. Mantovani, A., Allavena, P., Sica, A. & Balkwill, F. Cancer-related inflammation. Nature 454, 436–444 (2008)
    Article ADS CAS Google Scholar
  6. Grivennikov, S. I., Greten, F. R. & Karin, M. Immunity, inflammation, and cancer. Cell 140, 883–899 (2010)
    Article CAS Google Scholar
  7. Schreiber, R. D., Old, L. J. & Smyth, M. J. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331, 1565–1570 (2011)
    Article ADS CAS Google Scholar
  8. Galon, J. et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313, 1960–1964 (2006)
    Article ADS CAS Google Scholar
  9. Tosolini, M. et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res. 71, 1263–1271 (2011)
    Article CAS Google Scholar
  10. Brenchley, J. M. & Douek, D. C. Microbial translocation across the GI tract. Annu. Rev. Immunol. 30, 149–173 (2012)
    Article CAS Google Scholar
  11. McKenzie, B. S., Kastelein, R. A. & Cua, D. J. Understanding the IL-23-IL-17 immune pathway. Trends Immunol. 27, 17–23 (2006)
    Article CAS Google Scholar
  12. Langowski, J. L. et al. IL-23 promotes tumour incidence and growth. Nature 442, 461–465 (2006)
    Article ADS CAS Google Scholar
  13. Hinoi, T. et al. Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res. 67, 9721–9730 (2007)
    Article CAS Google Scholar
  14. Sawa, S. et al. RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nature Immunol. 12, 320–326 (2011)
    Article ADS CAS Google Scholar
  15. Medzhitov, R. Recognition of microorganisms and activation of the immune response. Nature 449, 819–826 (2007)
    Article ADS CAS Google Scholar
  16. Rakoff-Nahoum, S. & Medzhitov, R. Regulation of spontaneous intestinal tumorigenesis through the adaptor protein MyD88. Science 317, 124–127 (2007)
    Article ADS CAS Google Scholar
  17. Van der Sluis, M. et al. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131, 117–129 (2006)
    Article CAS Google Scholar
  18. Velcich, A. et al. Colorectal cancer in mice genetically deficient in the mucin Muc2. Science 295, 1726–1729 (2002)
    Article ADS CAS Google Scholar
  19. Rothwell, P. M. et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 377, 31–41 (2011)
    Article CAS Google Scholar
  20. Wang, X., Tully, O., Ngo, B., Zitin, M. & Mullin, J. M. Epithelial tight junctional changes in colorectal cancer tissues. Sci. World J. 11, 826–841 (2011)
    Article CAS Google Scholar
  21. Tanaka, T. et al. Dextran sodium sulfate strongly promotes colorectal carcinogenesis in Apc(Min/+) mice: inflammatory stimuli by dextran sodium sulfate results in development of multiple colonic neoplasms. Int. J. Cancer 118, 25–34 (2006)
    Article CAS Google Scholar
  22. Meira, L. B. et al. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J. Clin. Invest. 118, 2516–2525 (2008)
    CAS PubMed PubMed Central Google Scholar
  23. Newman, J. V., Kosaka, T., Sheppard, B. J., Fox, J. G. & Schauer, D. B. Bacterial infection promotes colon tumorigenesis in Apc(Min/+) mice. J. Infect. Dis. 184, 227–230 (2001)
    Article CAS Google Scholar
  24. Wu, S. et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nature Med. 15, 1016–1022 (2009)
    Article CAS Google Scholar
  25. Dove, W. F. et al. Intestinal neoplasia in the ApcMin mouse: independence from the microbial and natural killer (beige locus) status. Cancer Res. 57, 812–814 (1997)
    CAS PubMed Google Scholar
  26. Yang, L. & Pei, Z. Bacteria, inflammation, and colon cancer. World J. Gastroenterol. 12, 6741–6746 (2006)
    Article CAS Google Scholar
  27. Garrett, W. S. et al. Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. Cancer Cell 16, 208–219 (2009)
    Article CAS Google Scholar
  28. Zhou, L. et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nature Immunol. 8, 967–974 (2007)
    Article CAS Google Scholar
  29. Ivanov, I. I. et al. Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. Cell Host Microbe 4, 337–349 (2008)
    Article CAS Google Scholar
  30. Barker, N. et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457, 608–611 (2009)
    Article ADS CAS Google Scholar
  31. Lennard-Jones, J. E. Classification of inflammatory bowel disease. Scand. J. Gastroenterol. Suppl. 1702–6 (1989)
  32. Bond, J. H. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Practice Parameters Committee of the American College of Gastroenterology. Am. J. Gastroenterol. 95, 3053–3063 (2000)
    Article CAS Google Scholar
  33. Winawer, S. J. & Zauber, A. G. The advanced adenoma as the primary target of screening. Gastrointest. Endosc. Clin. N. Am. 12, 1–9 (2002)
    Article Google Scholar
  34. Liu, P., Jenkins, N. A. & Copeland, N. G. A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res. 13, 476–484 (2003)
    Article CAS Google Scholar
  35. Ghilardi, N. et al. Compromised humoral and delayed-type hypersensitivity responses in IL-23-deficient mice. J. Immunol. 172, 2827–2833 (2004)
    Article CAS Google Scholar
  36. Ye, P. et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med. 194, 519–527 (2001)
    Article CAS Google Scholar
  37. Awasthi, A. et al. Cutting edge: IL-23 receptor gfp reporter mice reveal distinct populations of IL-17-producing cells. J. Immunol. 182, 5904–5908 (2009)
    Article CAS Google Scholar
  38. Kirkland, D. et al. B cell-intrinsic MyD88 signaling prevents the lethal dissemination of commensal bacteria during colonic damage. Immunity 36, 228–238 (2012)
    Article CAS Google Scholar
  39. Kawai, T., Adachi, O., Ogawa, T., Takeda, K. & Akira, S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11, 115–122 (1999)
    Article CAS Google Scholar
  40. Hoshino, K. et al. Cutting edge: generation of IL-18 receptor-deficient mice: evidence for IL-1 receptor-related protein as an essential IL-18 binding receptor. J. Immunol. 162, 5041–5044 (1999)
    CAS PubMed Google Scholar
  41. Grivennikov, S. et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell 15, 103–113 (2009)
    Article CAS Google Scholar
  42. Kim, P. et al. In vivo wide-area cellular imaging by side-view endomicroscopy. Nature Methods 7, 303–305 (2010)
    Article CAS Google Scholar
  43. Hung, K. E. et al. Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment. Proc. Natl Acad. Sci. USA 107, 1565–1570 (2010)
    Article ADS CAS Google Scholar
  44. Chen, G. Y., Shaw, M. H., Redondo, G. & Nunez, G. The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. Cancer Res. 68, 10060–10067 (2008)
    Article CAS Google Scholar

Download references

Acknowledgements

We thank eBioscience, GeneTex, Santa Cruz, BioLegend and Cell Signaling for antibodies; Genentech and Amgen for Il23 −/− and Il17ra −/− mice, respectively, and S. Reid and E. Southon for the help in generating _Il23r_F/F mice. This work was supported by Crohn’s and Colitis Foundation of America (Career Development Award number 2693), NIH/National Institute of Diabetes and Digestive and Kidney Diseases (K99-DK088589) and a University of California, San Diego, Digestive Disease Research Development Center Pilot Grant (DK080506) to S.I.G.; Croucher Foundation and China Postdoctoral Science Foundation (20110490919) to K.W.; Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation to K.T.; SPAR Austria to C.D.; NIH (R01CA082223) to E.R.F.; and NIH (AI043477; DK035108) and American Association for Cancer Research (07-60-21-KARI) grants to M.K., who is an American Cancer Society Research Professor. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Author notes

  1. Sergei I. Grivennikov and Kepeng Wang: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Pharmacology and Pathology, Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA,
    Sergei I. Grivennikov, Kepeng Wang, Dominik Jauch, Koji Taniguchi, Guann-Yi Yu & Michael Karin
  2. Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, No. 1120, Lianhua Road, Shenzhen, Guangdong Province, China,
    Kepeng Wang
  3. La Jolla Institute for Allergy and Immunology, La Jolla, 92093, California, USA
    Daniel Mucida & Hilde Cheroutre
  4. Laboratory of Mucosal Immunology, The Rockefeller University, New York, 10065, New York, USA
    Daniel Mucida
  5. Cancer and Inflammation Program, Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, 21702-1201, Maryland, USA
    C. Andrew Stewart & Giorgio Trinchieri
  6. Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA,
    Bernd Schnabl, Christoph H. Österreicher & Lars Eckmann
  7. Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan,
    Koji Taniguchi
  8. Institute of Pharmacology, Center for Physiology and Pharmacology Medical University of Vienna, Vienna, Austria
    Christoph H. Österreicher
  9. Department of Medicine, Tufts Medical Center, Boston, 02111, Massachusetts, USA
    Kenneth E. Hung
  10. Department of Internal Medicine, Oberndorf Hospital, Paracelsus Medical University, Salzburg, Austria
    Christian Datz
  11. Departments of Internal Medicine, Human Genetics and Pathology, University of Michigan Medical School, Ann Arbor, 48109, Michigan, USA
    Ying Feng & Eric R. Fearon
  12. Seattle Children’s Research Institute, Seattle, 98105, Washington, USA
    Mohamed Oukka
  13. Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health, Frederick, 21702-1201, Maryland, USA
    Lino Tessarollo
  14. Department of Molecular Virology, Immunology & Medical Genetics, Ohio State University Comprehensive Cancer Center, Wexner Medical Center, Columbus, 43210, Ohio, USA
    Vincenzo Coppola
  15. Department of Immunology, University of Texas Southwestern Medical Center at Dallas, Dallas, 75390, Texas, USA
    Felix Yarovinsky

Authors

  1. Sergei I. Grivennikov
  2. Kepeng Wang
  3. Daniel Mucida
  4. C. Andrew Stewart
  5. Bernd Schnabl
  6. Dominik Jauch
  7. Koji Taniguchi
  8. Guann-Yi Yu
  9. Christoph H. Österreicher
  10. Kenneth E. Hung
  11. Christian Datz
  12. Ying Feng
  13. Eric R. Fearon
  14. Mohamed Oukka
  15. Lino Tessarollo
  16. Vincenzo Coppola
  17. Felix Yarovinsky
  18. Hilde Cheroutre
  19. Lars Eckmann
  20. Giorgio Trinchieri
  21. Michael Karin

Contributions

S.G. and M.K. conceived the project. S.I.G., K.W., D.M., B.S., D.J., K.T., G.Y.Y., C.O., Y.F. and K.E.H. performed the experiments. S.I.G., K.W., D.M., D.J., H.C., L.E. and M.K. analysed data. C.A.S., V.C., L.T. and G.T. generated _Il23r_F/F mice. M.O. and F.Y. provided Il23r gfp/gfp and _Tlr2,4,9_−/− bone marrow, respectively, and Y.F. and E.R.F. provided CPC-APC mice and tissues from _Cdx2_ERT-Cre-APC mice. C.A.S., E.R.F., H.C. and G.T. provided conceptual advice. C.D. collected and provided human specimens. S.I.G., K.W. and M.K. wrote the manuscript, with all authors contributing to the writing and providing advice.

Corresponding author

Correspondence toMichael Karin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Table 1 and Supplementary Figures 1-11. Supplementary Figs 1e, 2b and 8a were corrected on 07 November 2012. (PDF 2192 kb)

PowerPoint slides

Rights and permissions

About this article

Cite this article

Grivennikov, S., Wang, K., Mucida, D. et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth.Nature 491, 254–258 (2012). https://doi.org/10.1038/nature11465

Download citation