Immunotherapy for hepatocellular carcinoma.

Despite significant research efforts, only a few treatment approaches have been developed for hepatocellular carcinoma (HCC). In recent years, immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies) have exhibited potential therapeutic effects for advanced HCC. With the development of gene-editing technologies, gene-sequencing technologies, big data strategies, and artificial intelligence algorithms, engineered immune cell infusion and personalized cancer vaccine therapy have emerged as important directions for anti-HCC treatment. Combining different immunotherapies or combining immunotherapies with conventional therapeutic approaches may provide synergistic effects and facilitate the development of personalized medicine. In this study, we provide an overview of the liver immunoanatomy, the potential immune mechanisms of HCC, and current (pre)clinical developments in this field.

Zongyi Y ，Xiaowu L 《-》

Immune checkpoint inhibitors for hepatocellular carcinoma.

The position of immunotherapy as a pillar of systemic cancer treatment has been firmly established over the past decade. Immune checkpoint inhibitors are a welcome option for patients with different malignancies. This is in part because they offer the possibility of durable benefit, even for patients who have failed other treatment modalities. The recent demonstration that immunotherapy is effective for patients with hepatocellular carcinoma (HCC) is a milestone in the history of this recalcitrant disease. The treatment of HCC has been a challenge, and for many years was limited to the tyrosine kinase inhibitor sorafenib and to several novel tyrosine kinase inhibitors that have shown efficacy and have been approved. The current role of immune checkpoint inhibitors in the management of HCC, and how this role is likely to evolve in the years ahead, are key. Other than efforts evaluating single checkpoint inhibitors, potential combination strategies, including combinations with existing local and systemic approaches, including novel therapies are evolving. This is understandably of special interest considering the potential unique immune system of the liver, which may impact the use of immunotherapy in patients with HCC going forward, and how can it be enhanced further.

El Dika I ，Khalil DN ，Abou-Alfa GK 《-》

Immune checkpoint blockade in advanced hepatocellular carcinoma: an update and critical review of ongoing clinical trials.

Harding JJ 《-》

Combining Tumor Vaccination and Oncolytic Viral Approaches with Checkpoint Inhibitors: Rationale, Pre-Clinical Experience, and Current Clinical Trials in Malignant Melanoma.

Cavalcante L ，Chowdhary A ，Sosman JA ，Chandra S ... -  《-》

Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma.

Immune checkpoint inhibitor (ICI) therapy targeting anti-programmed cell death-1 (anti-PD-1) or its ligand (anti-PD-L1) is the backbone of numerous combination regimens aimed at improving the objective response and survival of patients with hepatocellular carcinoma (HCC). Clinical trials of immuno-oncology regimens in other cancer types have shed light on issues of study design, including how to choose candidate regimens based on early-phase trial results, statistical considerations in trials with multiple primary endpoints, and the importance of predictive biomarkers. In this review, the updated data from early-phase trials of combination immunotherapy for HCC are summarised. Since the most extensively tested combination regimens for advanced HCC comprise anti-PD-1/anti-PD-L1 agents plus antiangiogenic agents, the relative benefit and antitumor mechanism of antiangiogenic multikinase inhibitors versus specific VEGF/VEGFR inhibitors are discussed. Other critical issues in the development of combination immunotherapy, including optimal management of immune-related adverse events and the value of ICI therapy in combination with locoregional treatment for HCC, are also explored.

Cheng AL ，Hsu C ，Chan SL ，Choo SP ，Kudo M ... -  《-》