Display options
Cite
Owusu Sekyere S, Schlevogt B, Mettke F, et al. HCC Immune Surveillance and Antiviral Therapy of Hepatitis C Virus Infection. Liver Cancer. 2018;8(1):41-65doi: 10.1159/000490360.
Owusu Sekyere, S., Schlevogt, B., Mettke, F., Kabbani, M., Deterding, K., Wirth, T. C., Vogel, A., Manns, M. P., Falk, C. S., Cornberg, M., & Wedemeyer, H. (2019). HCC Immune Surveillance and Antiviral Therapy of Hepatitis C Virus Infection. Liver cancer, 8(1), 41-65. https://doi.org/10.1159/000490360
Owusu Sekyere, Solomon, et al. "HCC Immune Surveillance and Antiviral Therapy of Hepatitis C Virus Infection." Liver cancer vol. 8,1 (2019): 41-65. doi: https://doi.org/10.1159/000490360
Owusu Sekyere S, Schlevogt B, Mettke F, Kabbani M, Deterding K, Wirth TC, Vogel A, Manns MP, Falk CS, Cornberg M, Wedemeyer H. HCC Immune Surveillance and Antiviral Therapy of Hepatitis C Virus Infection. Liver Cancer. 2019 Feb;8(1):41-65. doi: 10.1159/000490360. Epub 2018 Jul 18. PMID: 30815394; PMCID: PMC6388568.
Copy Download .nbib Format: NLM
Share it on

Liver Cancer. 2019 Feb;8(1):41-65. doi: 10.1159/000490360. Epub 2018 Jul 18.

HCC Immune Surveillance and Antiviral Therapy of Hepatitis C Virus Infection.

Liver cancer

Solomon Owusu Sekyere, Bernhard Schlevogt, Friederike Mettke, Mohammad Kabbani, Katja Deterding, Thomas Christian Wirth, Arndt Vogel, Michael Peter Manns, Christine Susanne Falk, Markus Cornberg, Heiner Wedemeyer

Affiliations

  1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
  2. Department of Medicine B, Gastroenterology and Hepatology, University Hospital Münster, Münster, Germany.
  3. TTU-IICH, German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover-Braunschweig, Germany.
  4. Department of General, Abdominal, and Transplant Surgery, Hannover Medical School, Hanover, Germany.
  5. Institute of Transplantation Immunology (IFB-Tx), Hannover Medical School, Hannover, Germany.
  6. Department of Gastroenterology and Hepatology, Essen University Hospital, University of Duisburg-Essen, Essen, Germany.

PMID: 30815394 PMCID: PMC6388568 DOI: 10.1159/000490360

Abstract

OBJECTIVE: HCV clearance by current antiviral therapies improves clinical outcomes but falls short in eliminating the risk for hepatocellular carcinoma (HCC) emergence. As the HCC immune surveillance establishment is vital for the control of neoplastic development and growth, we investigated its correlation with on-/post-treatment HCC emergence, and further analyzed the influence of viral eradication on this setup in patients with HCV-related liver cirrhosis.

DESIGN: PBMC isolated at baseline and longitudinally during therapy were analyzed for tumor-associated antigen (TAA)-specific CD8+ T cell responses against glypican-3 overlapping peptides in vitro using high-definition flow cytometry. Multianalyte profiling of fifty soluble inflammatory mediators (SIM) in the plasma was also performed using Luminex-based multiplex technology.

RESULTS: Cirrhosis patients were characterized by an altered profile of distinct SIMs at baseline. At this time point, immune-surveilling T cells targeting specific HCC-associated antigens were readily detectable in HCV-free cirrhosis patients whilst being rather weak in such patients who further developed HCC upon virus eradication. Therapy-induced cure of HCV infection analogously reduced the strength of the prevailing HCC immune surveillance machinery, particularly by CD8+ T cells in cirrhosis patients. These results were further validated by T cell reactivities to six immuno-dominant HCC-associated HLA-A2-restricted epi-topes. Further, we demonstrated that this phenomenon was likely orchestrated by alterations in SIMs - with evidence of IL-12 being a major culprit.

CONCLUSION: Given the relationship between the baseline HCC-specific immune surveilling T cell responses and therapy-associated HCC emergence, and the impact of HCV clearance on its strength and magnitude, we recommend a continued HCC screening in cirrhotic HCV patients despite HCV resolution.

Keywords: Hepatitis C; Hepatocellular carcinoma; IFN-free therapy; Immune surveillance; T cells

References

  1. Eur J Immunol. 1999 Feb;29(2):548-55 - PubMed
  2. Int J Cancer. 2006 Mar 1;118(5):1194-204 - PubMed
  3. J Immunother. 2007 May-Jun;30(4):425-37 - PubMed
  4. Hepatology. 2008 Dec;48(6):1821-33 - PubMed
  5. J Immunol Methods. 2009 Mar 15;342(1-2):33-48 - PubMed
  6. Gastroenterology. 2009 Aug;137(2):682-90 - PubMed
  7. Br J Cancer. 2010 Feb 16;102(4):748-53 - PubMed
  8. Curr Immunol Rev. 2005 Jun;1(2):119-137 - PubMed
  9. Science. 2011 Mar 25;331(6024):1565-70 - PubMed
  10. Neoplasia. 2011 Aug;13(8):735-47 - PubMed
  11. Hepatology. 2013 Apr;57(4):1448-57 - PubMed
  12. Hepatology. 2014 Apr;59(4):1415-26 - PubMed
  13. J Pathol. 2014 Jan;232(2):199-209 - PubMed
  14. Hepatology. 2014 Apr;59(4):1232-4 - PubMed
  15. Semin Cancer Biol. 2014 Jun;26:78-88 - PubMed
  16. J Viral Hepat. 2014 May;21 Suppl 1:34-59 - PubMed
  17. J Clin Invest. 2014 Aug;124(8):3352-63 - PubMed
  18. Clin Cancer Res. 2014 Dec 15;20(24):6418-28 - PubMed
  19. Lancet. 2015 Jan 10;385(9963):117-71 - PubMed
  20. J Clin Oncol. 2015 Jun 10;33(17):1974-82 - PubMed
  21. Gastroenterology. 2015 Oct;149(4):1042-52 - PubMed
  22. Front Immunol. 2015 Jun 10;6:270 - PubMed
  23. J Viral Hepat. 2016 Apr;23(4):305-15 - PubMed
  24. J Hepatol. 2016 Oct;65(4):719-726 - PubMed
  25. Nat Rev Gastroenterol Hepatol. 2016 Oct;13(10):561-2 - PubMed
  26. J Infect Dis. 2016 Dec 15;214(12):1965-1974 - PubMed
  27. J Hepatol. 2017 May;66(5):888-896 - PubMed
  28. Front Immunol. 2017 Jan 11;7:690 - PubMed
  29. J Hepatol. 2017 Jun;66(6):1138-1148 - PubMed
  30. Semin Liver Dis. 2017 May;37(2):109-118 - PubMed
  31. Lancet. 2017 Jun 24;389(10088):2492-2502 - PubMed
  32. Med Res Rev. 2018 Mar;38(2):741-767 - PubMed
  33. Gastroenterology. 2017 Oct;153(4):996-1005.e1 - PubMed
  34. Hepatology. 2019 Feb;69(2):487-497 - PubMed
  35. Oncotarget. 2017 May 16;8(32):52866-52876 - PubMed
  36. J Hepatol. 2017 Sep 5;: - PubMed
  37. Aliment Pharmacol Ther. 2018 Jan;47(1):104-113 - PubMed
  38. Gastroenterology. 2018 Feb;154(3):515-517.e3 - PubMed
  39. Aliment Pharmacol Ther. 2018 Feb;47(4):516-525 - PubMed
  40. Blood. 1994 Dec 15;84(12):4008-27 - PubMed
  41. Eur J Immunol. 1996 Mar;26(3):659-68 - PubMed

Publication Types