HBV-Induced Immune Imbalance in the Development of HCC
Chronic hepatitis B virus (HBV) infection is one of the high-risk factors for human HCC. Despite the integration of virus DNA and the oncoprotein HBx, chronic necroinflammation and hepatocellular regeneration account for hepatocarcinogenesis. As a non-cytopathic virus, HBV is extensively recognized...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02048/full |
| _version_ | 1818839848717385728 |
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| author | Yongyan Chen Yongyan Chen Zhigang Tian Zhigang Tian |
| author_facet | Yongyan Chen Yongyan Chen Zhigang Tian Zhigang Tian |
| author_sort | Yongyan Chen |
| collection | DOAJ |
| description | Chronic hepatitis B virus (HBV) infection is one of the high-risk factors for human HCC. Despite the integration of virus DNA and the oncoprotein HBx, chronic necroinflammation and hepatocellular regeneration account for hepatocarcinogenesis. As a non-cytopathic virus, HBV is extensively recognized to mediate chronic liver damage through abnormal immune attack. However, the mechanisms driving HBV infection to HCC are poorly understood. During chronic HBV infection in humans, the adaptive immunity changes from immune tolerance to progressive immune activation, inactivation, reactivation and exhaustion, all of which may be the immune pathogenic factors for the development of HCC. Recently, the immunopathogenic mechanisms were described in mouse HBV-induced HCC models, which is absolutely dependent on the presence of HBV-specific T cell response and NK cell-derived IFN-γ, findings which are consistent with the observations from CHB and HCC patients. In this review, we summarize recent research progression on the HBV-specific CD8+ T cells, and also CD4+ T cells, B cells and non-specific immune cells and molecules underlying chronic HBV infection and eventual HCC development to demonstrate the pathogenesis of HBV-induced immune imbalance. Based on the progression, we discussed the potential of immune-based therapies and their challenges in the treatment of HBV-related HCC, including the checkpoint inhibition, genetically modified T cell transfer, therapeutic vaccines and metabolic modulation. |
| first_indexed | 2024-12-19T04:00:49Z |
| format | Article |
| id | doaj.art-223fbb15cfa1411dba36123123fa1171 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T04:00:49Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-223fbb15cfa1411dba36123123fa11712022-12-21T20:36:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-08-011010.3389/fimmu.2019.02048478201HBV-Induced Immune Imbalance in the Development of HCCYongyan Chen0Yongyan Chen1Zhigang Tian2Zhigang Tian3Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Molecular Medicine, School of Life Sciences, University of Science and Technology of China, Hefei, ChinaInstitute of Immunology, University of Science and Technology of China, Hefei, ChinaHefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, Division of Molecular Medicine, School of Life Sciences, University of Science and Technology of China, Hefei, ChinaInstitute of Immunology, University of Science and Technology of China, Hefei, ChinaChronic hepatitis B virus (HBV) infection is one of the high-risk factors for human HCC. Despite the integration of virus DNA and the oncoprotein HBx, chronic necroinflammation and hepatocellular regeneration account for hepatocarcinogenesis. As a non-cytopathic virus, HBV is extensively recognized to mediate chronic liver damage through abnormal immune attack. However, the mechanisms driving HBV infection to HCC are poorly understood. During chronic HBV infection in humans, the adaptive immunity changes from immune tolerance to progressive immune activation, inactivation, reactivation and exhaustion, all of which may be the immune pathogenic factors for the development of HCC. Recently, the immunopathogenic mechanisms were described in mouse HBV-induced HCC models, which is absolutely dependent on the presence of HBV-specific T cell response and NK cell-derived IFN-γ, findings which are consistent with the observations from CHB and HCC patients. In this review, we summarize recent research progression on the HBV-specific CD8+ T cells, and also CD4+ T cells, B cells and non-specific immune cells and molecules underlying chronic HBV infection and eventual HCC development to demonstrate the pathogenesis of HBV-induced immune imbalance. Based on the progression, we discussed the potential of immune-based therapies and their challenges in the treatment of HBV-related HCC, including the checkpoint inhibition, genetically modified T cell transfer, therapeutic vaccines and metabolic modulation.https://www.frontiersin.org/article/10.3389/fimmu.2019.02048/fullHBVimmune dysfunctionHCCadaptive immunityinnate immunity |
| spellingShingle | Yongyan Chen Yongyan Chen Zhigang Tian Zhigang Tian HBV-Induced Immune Imbalance in the Development of HCC Frontiers in Immunology HBV immune dysfunction HCC adaptive immunity innate immunity |
| title | HBV-Induced Immune Imbalance in the Development of HCC |
| title_full | HBV-Induced Immune Imbalance in the Development of HCC |
| title_fullStr | HBV-Induced Immune Imbalance in the Development of HCC |
| title_full_unstemmed | HBV-Induced Immune Imbalance in the Development of HCC |
| title_short | HBV-Induced Immune Imbalance in the Development of HCC |
| title_sort | hbv induced immune imbalance in the development of hcc |
| topic | HBV immune dysfunction HCC adaptive immunity innate immunity |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02048/full |
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