Immunological Basis of Genesis of Hepatocellular Carcinoma: Unique Challenges and Potential Opportunities through Immunomodulation
Abstract
:1. Introduction
2. Immune Response and Tolerance in the Hepatic Parenchyma
3. Tumour Microenvironment and Immunosuppression in HCC
4. HCC Tumour Microenvironment and Changes in Cytokines Milieu
5. HCC Tumour Microenvironment Immunomodulation
5.1. HCC Tumour Microenvironment Immunomodulation through Radiofrequency Application
5.2. HCC Tumour Microenvironment Immunomodulation through Immunotherapy
5.3. HCC Tumour Microenvironment Immunomodulation through Combined Approach
6. Future Perspectives and Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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Name | Study | Detail | Phase | Sample | Primary Endpoint | Status |
---|---|---|---|---|---|---|
CTLA-4 | NCT01853618 | Tremelimumab with ablation | II | 32 | PR—26% Median TTP—7.4 mon Median OS—12.3 mon | Completed |
NCT02519348 | Tremelimumab with Durvalumab | II | 144 | Safety and tolerability | Ongoing | |
PD-1 | NCT01658878 | Nivolumab vs. Placebo | I/II | 262 | OR—20% DOR—9.9 mo | Completed |
NCT02576509 | Nivolumab vs. Sorafenib | III | 726 | Overall survival | Completed (Results awaited) | |
NCT02702414 | Pembrolizumab vs. Sorafenib | II | 104 | OS—26% Median OS—12.9 mon | Completed | |
NCT02702401 | Pembrolizumab vs. Placebo | III | 408 | Progression-free survival, Overall survival | Ongoing | |
NCT03062358 | Pembrolizumab vs. Placebo | III | 330 | Overall survival | Ongoing | |
NCT03383458 | Nivolumab vs. Placebo | III | 530 | Recurrence-free survival | Ongoing | |
NCT02512773 | Tislelizumab vs. Sorafenib | III | 660 | Overall survival | Ongoing | |
PD-L1 | NCT03298451 | Durvalumab vs. Durvalumab + Tremelimumab (regimen 1) vs. Durvalumab + Tremelimumab (regimen 2) vs. Sorafenib | III | 1200 | Overall survival | Ongoing |
NCT03434379 | Atezolizumab + Bevacizumab vs. Sorafenib | III | 480 | Overall survival | Ongoing |
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Jayant, K.; Habib, N.; Huang, K.W.; Podda, M.; Warwick, J.; Arasaradnam, R. Immunological Basis of Genesis of Hepatocellular Carcinoma: Unique Challenges and Potential Opportunities through Immunomodulation. Vaccines 2020, 8, 247. https://doi.org/10.3390/vaccines8020247
Jayant K, Habib N, Huang KW, Podda M, Warwick J, Arasaradnam R. Immunological Basis of Genesis of Hepatocellular Carcinoma: Unique Challenges and Potential Opportunities through Immunomodulation. Vaccines. 2020; 8(2):247. https://doi.org/10.3390/vaccines8020247
Chicago/Turabian StyleJayant, Kumar, Nagy Habib, Kai W. Huang, Mauro Podda, Jane Warwick, and Ramesh Arasaradnam. 2020. "Immunological Basis of Genesis of Hepatocellular Carcinoma: Unique Challenges and Potential Opportunities through Immunomodulation" Vaccines 8, no. 2: 247. https://doi.org/10.3390/vaccines8020247