HCC Immune Surveillance and Antiviral Therapy of Hepatitis C Virus Infection

GND
1078022917
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Owusu Sekyere, Solomon;
GND
1207881414
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Schlevogt, Bernhard;
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Mettke, Friederike;
GND
1061212920
ORCID
0000-0001-9556-384X
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Kabbani, Mohammad;
GND
132829037
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Deterding, Katja;
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Wirth, Thomas Christian;
GND
12366960X
ORCID
0000-0003-0560-5538
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Vogel, Arndt;
GND
129973890
ORCID
0000-0002-4485-8856
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Manns, Michael P.;
GND
173109195
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Falk, Christine Susanne;
GND
122338413
ORCID
0000-0002-9141-8001
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Cornberg, Markus;
GND
124865798
LSF
60121
Affiliation
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
Wedemeyer, Heiner

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 epi­topes. 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.

Cite

Citation style:
Could not load citation form.

Rights

License Holder:

© 2018 S. Karger AG, Basel

Use and reproduction:
All rights reserved

Export