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Updated: Feb 11, 2026
Mass Cytometry Analysis of Systemic and Local Immune Responses in Hepatocellular Carcinoma
Published on: April 25, 2025
Immune checkpoint blockade for the treatment of human hepatocellular carcinoma
Naoshi Nishida1, Masatoshi Kudo1
1Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Abstract:
Hepatocellular carcinoma (HCC) is one of the most common cancers with a high recurrence rate. Currently, tyrosine kinase inhibitors (TKIs) are the first-line treatment for cases refractory to conventional therapies. However, the acquisition of somatic mutations can result in TKI resistance. Clinical evidence suggests that acquired immunity contributes to the suppression of tumor recurrence, indicating the potential of induced antitumor immune reaction for the treatment of HCC. Recently, immune checkpoint inhibitors have become available for the treatment of malignancies. They are effective regardless of the response to prior therapies and a durable effect can be expected, which should be attributed to an adaptive immunity to HCC components. The results of phase I/II trials of nivolumab, an anti-programmed cell death-1 antibody, showed that 20% of patients showed objective response and that nivolumab was effective regardless of prior sorafenib treatment and viral status. Nivolumab received expedited Food and Drug Administration approval in 2017 for the treatment of advanced HCC after failure or intolerance to sorafenib. However, the majority of the patients remain refractory, likely due to the solid immune suppressive status, which involves many stromal cells, humoral mediators, and suppressive checkpoint molecules. Therefore, current clinical trials are focusing on how immunosuppressive conditions in HCC might be overcome using immune checkpoint inhibitors in combination with different types of immune checkpoint blockades, TKIs, and other conventional treatments. The development of immune checkpoint inhibitors is rapidly progressing and these inhibitors are likely to be key agents for HCC treatment in the near feature.
Insights
Hepatocellular carcinoma (HCC) treatment is advancing with immune checkpoint inhibitors, offering new hope for patients resistant to traditional therapies like tyrosine kinase inhibitors (TKIs). Research explores combining these therapies to overcome tumor-induced immune suppression.
Area of Science:
- Hepatology
- Oncology
- Immunology
Background:
- Hepatocellular carcinoma (HCC) presents a significant global health challenge due to its high incidence and recurrence rates.
- Current first-line treatments, such as tyrosine kinase inhibitors (TKIs), often face resistance stemming from acquired somatic mutations.
- Emerging evidence highlights the role of the immune system in suppressing HCC recurrence, suggesting immunotherapy as a promising therapeutic avenue.
Purpose of the Study:
- To review the current landscape of HCC treatment, focusing on the emergence and potential of immune checkpoint inhibitors (ICIs).
- To discuss the mechanisms of TKI resistance and the rationale for leveraging adaptive immunity against HCC.
- To explore ongoing clinical trials investigating combination strategies to overcome the immunosuppressive tumor microenvironment in HCC.
Main Methods:
- Review of clinical trial data and scientific literature on HCC treatments, including TKIs and ICIs.
- Analysis of nivolumab (an anti-PD-1 antibody) efficacy in advanced HCC patients.
- Examination of the immunosuppressive factors within the HCC tumor microenvironment.
Main Results:
- Immune checkpoint inhibitors, like nivolumab, demonstrate objective responses in a subset of HCC patients, irrespective of prior sorafenib treatment or viral status.
- Nivolumab received FDA approval for advanced HCC post-sorafenib failure, indicating clinical utility.
- Despite successes, a majority of patients remain refractory, underscoring the challenge of the profoundly immunosuppressive HCC microenvironment.
Conclusions:
- Immune checkpoint inhibitors represent a significant advancement in HCC therapy, offering durable responses through adaptive immunity.
- Overcoming the solid immune-suppressive status in HCC is critical and is being addressed through combination therapies.
- ICIs are poised to become pivotal agents in the future treatment of HCC, with ongoing research focused on optimizing their use.
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