Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy
Abstract
:1. Introduction
2. Molecular Characterization and Typing of HBV-HCC
2.1. Molecular Characterization of HBV-HCC
2.2. Typing of HBV-HCC
3. Occurrence and Development of HBV-HCC
3.1. Direct Oncogenic Mechanism of HBV
3.1.1. Insertion Mutations
3.1.2. HBV Causes Genomic Instability
3.1.3. Prolonged Expression of Viral Proteins Affects Cell Functioning
3.2. Immune-Mediated Indirect Oncogenic Mechanisms of HBV
4. Current Status of Treatment of HBV-HCC
4.1. Antiviral Therapy
4.2. Surgical Excision and Radiofrequency Therapy
4.3. Liver Transplantation
4.4. Radiotherapy and Chemotherapy
4.5. Tyrosine Kinase Inhibitor Therapy
4.6. Immunotherapy
5. Immune Checkpoint Inhibitors for the Treatment of HBV-HCC
5.1. Principle of Action of Immune Checkpoint Molecules in HBV-HCC and Targeted Inhibitors
5.1.1. Programmed Cell Death Protein 1 (PD-1)
5.1.2. Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4)
5.1.3. Lymphocyte Activation Gene 3 (LAG3)
5.1.4. T Cell Immunoglobulins and ITIM Domains (TIGIT)
5.1.5. T Cell Immunoglobulin Mucin 3 (TIM-3)
5.2. Advantages of Immune Checkpoint Inhibitors in the Treatment of HBV-HCC
5.3. Efficacy of Immune Checkpoint Inhibitors in the Treatment of HCC with Different Etiologies
6. Potential Immune Checkpoint Therapeutic Targets
6.1. HHLA2
6.2. CCR4
6.3. DDRs
6.4. IL-27/IL-27R
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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HBV Genotype | A | B | C | D | E | F | G | H | I | J (Putative) |
---|---|---|---|---|---|---|---|---|---|---|
Occurrence and development of HBV-HCC | Direct oncogenic mechanism of HBV-HCC | Insertion mutations | ||||||||
HBV causes genomic instability | ||||||||||
Prolonged expression of viral proteins affects cell function | ||||||||||
Indirect oncogenic mechanisms of HBV-HCC | Immune-mediated indirect oncogenic mechanisms of HBV |
Immune Checkpoint | Current FDA-Approved Inhibitors | No. of Ongoing Clinical Trials Related to HCC * | Hyperlinks and References |
---|---|---|---|
PD-1 | Nibolumab (FDA-approved for the treatment of HCC following sorafenib) | 88 | ClinicalTrials.gov [68,69] |
Pembrolizumab (FDA-approved for the treatment of HCC following sorafenib) | 76 | ClinicalTrials.gov [70] | |
Cemiplimab (FDA has not approved it for HCC treatment) | 4 | ClinicalTrials.gov | |
Dostarlimab (FDA-approved for treatment of unresectable liver cancer) | 1 | ClinicalTrials.gov | |
CTLA4 | Tremelimumab (FDA-approved for treatment of unresectable liver cancer) | 20 | ClinicalTrials.gov [71,72] |
Ipilimumab (FDA-approved for the treatment of hepatocellular carcinoma following sorafenib) | 22 | ClinicalTrials.gov [69] | |
LAG-3 | Relatlimab (FDA has not approved it for HCC treatment) | 4 | ClinicalTrials.gov [73] |
TIGIT | Tiragolumab has been granted breakthrough drug status by the FDA, and Vibostolimab has initiated clinical trials related to HCC | 2 | ClinicalTrials.gov1 ClinicalTrials.gov2 |
TIM-3 | Cobolimab is undergoing a series of clinical trials | 1 | ClinicalTrials.gov |
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Zhang, J.; Hu, C.; Xie, X.; Qi, L.; Li, C.; Li, S. Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy. Vaccines 2023, 11, 614. https://doi.org/10.3390/vaccines11030614
Zhang J, Hu C, Xie X, Qi L, Li C, Li S. Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy. Vaccines. 2023; 11(3):614. https://doi.org/10.3390/vaccines11030614
Chicago/Turabian StyleZhang, Jin, Changwei Hu, Xiaoxiao Xie, Linzhi Qi, Chuanzhou Li, and Shangze Li. 2023. "Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy" Vaccines 11, no. 3: 614. https://doi.org/10.3390/vaccines11030614
APA StyleZhang, J., Hu, C., Xie, X., Qi, L., Li, C., & Li, S. (2023). Immune Checkpoint Inhibitors in HBV-Caused Hepatocellular Carcinoma Therapy. Vaccines, 11(3), 614. https://doi.org/10.3390/vaccines11030614