Strategic International Session4(JSGE)
Sat. November 4th   9:00 - 12:00   Room 11: Portopia Hotel South Wing Topaz
Immunopathogenesis of HBV and HCC
Tatsuya Kanto
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine
WHO set the target of the elimination of HBV and HCV by 2030. To attain this goal, deeper understanding of the immunopathogenesis of both viruses is needed. Unless eradicated, chronic hepatitis progresses to liver cirrhosis and hepatocellular carcinoma (HCC), which is impacted by the impairment of immune surveillance system.
Functional cure of HBV, or HBsAg loss, from chronically-infected patients is a clinical target of HCC risk reduction. In cases of acute resolving hepatitis, we demonstrated that sequential chemokine and cytokine activation is involved in HBsAg seroconversion, showing an active role of follicular-helper T cells(Tfh) and B cells. We showed that a novel TLR7 agonist is able to stimulate plasmacytoid DCs and B cells inducing Tfh and enhancing production of anti-HBs antibody. Currently, the development of novel anti-HBV therapy is underway using TLR7 agonist as an immune modulator.
Natural killer(NK) cells play a pivotal role in immune-surveillance against HCC. We identified some of signature NK cell receptors in HCC patients, ILT2 as an inhibitory and NKp46 as a stimulatory receptor, respectively. ILT2+CD56dimNKp46-negative NK cells, which are enriched in HCC tissue, exhibit lessor capacity of cytotoxicity/ADCC. ILT2 blockade restored the capacity of ILT2+CD56dimNK cells, suggesting that ILT2 serves as a therapeutic target against HCC.
A further comprehensive study of clinical samples is needed to improve our understanding of immune mechanisms associated with HBV and HCC control in the liver.
Index Term 1: HBV
Index Term 2: HCC
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