The Current Landscape of Immune Checkpoint Blockade in Hepatocellular Carcinoma: A Review
Matthias Pinter1, Rakesh K Jain2, Dan G Duda2
1Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Importance:
For more than a decade, sorafenib has been the only systemic treatment option for patients with advanced hepatocellular carcinoma (HCC). However, rapid progress over the past few years led to approval of other angiogenesis inhibitors and several immune checkpoint blockers (ICBs) that have been added to the treatment armamentarium for advanced HCC. Moreover, the recent success of a combination of bevacizumab with atezolizumab signals an important change in the front-line treatment of HCC.
Observations:
This review summarizes rapidly emerging clinical data on the promise and challenges of implementing ICBs in HCC and discusses the unmet need of biomarkers to predict response or resistance to therapy. Two strategies to target immunosuppression in tumors are also discussed: one proven (vascular endothelial growth factor pathway inhibition) and one currently under investigation (transforming growth factor-β pathway inhibition). The rationale and preliminary evidence on how their inhibition may reprogram the immunosuppressive milieu and enhance the efficacy of ICBs in HCC are reviewed.
Conclusion And Relevance:
The recent successes and failures of angiogenesis inhibitors and ICBs, alone and in combination, have provided important insights into how to implement this novel systemic therapy in HCC and led to new avenues to enhance immunotherapy efficacy in this disease.
Insights
New treatments, including angiogenesis inhibitors and immune checkpoint blockers (ICBs), are changing advanced hepatocellular carcinoma (HCC) care. Research explores biomarkers and combination therapies to improve immunotherapy effectiveness in HCC.
Area of Science:
- Hepatocellular Carcinoma (HCC) Treatment
- Cancer Immunotherapy
- Angiogenesis Inhibition
Background:
- Sorafenib was the sole systemic option for advanced HCC for over a decade.
- Recent advancements introduced new angiogenesis inhibitors and immune checkpoint blockers (ICBs).
- The combination of bevacizumab and atezolizumab marks a significant shift in first-line HCC treatment.
Purpose of the Study:
- To review emerging clinical data on immune checkpoint blockers (ICBs) in HCC.
- To discuss the need for biomarkers predicting response or resistance to HCC therapies.
- To explore strategies for targeting tumor immunosuppression, including VEGF and TGF-β pathways.
Main Methods:
- Review of rapidly emerging clinical data on ICBs in HCC.
- Discussion of biomarker needs for predicting therapy response.
- Analysis of strategies targeting tumor immunosuppression (VEGF and TGF-β pathways).
Main Results:
- Emerging data highlight the promise and challenges of ICBs in HCC treatment.
- Biomarkers are crucial for predicting patient response to novel HCC therapies.
- Inhibiting VEGF and TGF-β pathways shows potential to enhance ICB efficacy by modulating the tumor microenvironment.
Conclusions:
- Successes and failures of current therapies provide insights for HCC treatment implementation.
- Novel systemic therapies, including angiogenesis inhibitors and ICBs, are transforming HCC management.
- New strategies are emerging to enhance immunotherapy efficacy in advanced HCC.
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