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The progress of immune checkpoint therapy in primary liver cancer
Yimin Zheng1, Siwei Wang2, Jiabin Cai3
1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, PR China; Department of Liver Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
Abstract:
After years of in-depth research on immune checkpoints, therapeutic reversal of immune-exhaustion with immune checkpoint inhibitors (ICPIs) has been shown to be effective in primary liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma. The clinical development of novel ICPIs continues at a rapid pace, with more than 200 clinical trials of immunotherapeutic agents registered as of July 2021 for the treatment of liver cancer. In this review, we discussed the immune tolerance mechanism of liver cancer and the biological basis of immune checkpoints, focusing on the current status of ICPIs' development and clinical application. In addition, ICPIs combined with local resection, radiofrequency ablation, chemoembolization, and other molecular targeted drug therapies have shown better efficacy. Combined therapy based on multidisciplinary cooperation is the future direction of treatment in liver cancer.
Insights
Immune checkpoint inhibitors (ICPIs) show promise in treating liver cancer by reversing immune exhaustion. Combining ICPIs with other therapies offers improved efficacy and represents the future of liver cancer treatment.
Area of Science:
- Oncology
- Immunology
- Hepatology
Background:
- Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, often exhibits immune tolerance.
- Immune checkpoints play a crucial role in regulating immune responses within the tumor microenvironment.
Purpose of the Study:
- To review the immune tolerance mechanisms in liver cancer.
- To discuss the biological basis and clinical application of immune checkpoint inhibitors (ICPIs).
- To explore the efficacy of combination therapies for liver cancer.
Main Methods:
- Review of current literature on immune checkpoints and liver cancer.
- Analysis of clinical trial data for ICPIs in liver cancer treatment.
- Discussion of emerging combination therapeutic strategies.
Main Results:
- Therapeutic reversal of immune exhaustion using ICPIs is effective in primary liver cancers.
- Over 200 clinical trials for ICPIs in liver cancer were registered by July 2021.
- Combination therapies (ICPIs with resection, ablation, chemoembolization, targeted drugs) demonstrate enhanced efficacy.
Conclusions:
- Immune checkpoint inhibitors are a significant advancement in liver cancer treatment.
- Multidisciplinary combined therapy, integrating ICPIs with other modalities, is the future direction for liver cancer management.
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