Role of Immune Checkpoint Blockade in the Treatment for Human Hepatocellular Carcinoma

Nishida, Naoshi; Kudo, Masatoshi

doi:10.1159/000480258

Cited by 10 publications

(18 citation statements)

References 32 publications

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“…Notably, immune checkpoint inhibitors have proven effective in patients who are refractory to tyrosine kinase inhibitors (TKIs) such as sorafenib, and recently several blocking antibodies targeting PD-1 or CTLA-4 have shown promising results in advanced HCC patients who received previous treatment with sorafenib [20,28,72] . Compared to TKIs, immunotherapy has several advantages for the treatment of cancer, as its effects are not hampered by common mutations or neoantigen heterogeneity of tumor cells [28,73] . Therefore, immunooncology agent is effective regardless of the response to prior therapies, and also a durable response can be expected due to adaptive immunity to the cancer cells [74] .…”

Section: Immune Checkpoint Blockades In Hccmentioning

confidence: 99%

“…Also, the hepatitis B (HBV) and hepatitis C virus (HCV) infections, two major pathogens of HCC, have been shown to interfere with antiviral immunity via the immune checkpoint pathways [25][26][27] . Blocking these immune checkpoint molecules restores T cell function, which release the brakes on the anti-tumor immune surveillance, allowing the immune system to more effectively detect and kill the HCC tumor cells [2,20,28] .…”

Section: Introductionmentioning

confidence: 99%

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Cancer immuotherapy for hepatocellular carcinoma

Lee¹,

Oh²,

Kim³

et al. 2018

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Most hepatocellular carcinomas (HCCs) arise on a background of chronically inflamed liver, and thus are considered typical immunogenic cancers. Although there have been advances in treatment options for HCC, many patients still struggle with a limited chance of survival requiring further innovative approach. Especially for the advanced HCC, many other molecular targeted therapies had been evaluated without success. Based on the immunological mechanisms thought to be acting during HCC development, the effects of diverse immunomodulatory regimens such as therapeutic vaccination, immune checkpoint inhibitors, and adoptive cellular immunotherapy have been investigated. Notably, many strategies have been developed in adoptive cellular immunotherapy, including dendritic cells, cytotoxic T cells, natural killer cells, cytokine-induced killer (CIK) cells, and genetically engineered T cells. In recent clinical trials, adjuvant CIK cell immunotherapy increased progression free survival after curative treatment of HCC. Most recently, new immunomodulatory agents were introduced for oncological treatment, eventually leading to the clinical breakthrough of checkpoint inhibitors targeting cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1). To date, very promising published evidence with checkpoint inhibitors in HCC has been reported in the clinical trials with anti-CTLA-4 agent tremelimumab and a large phase II trial with anti-PD-1 agent nivolumab. Further investigations of immuno-oncology potentially popularized the applications of immunotherapy in the various stages of HCCs, and thus immune-based therapies are the promising innovative approach for patients with HCC. Hopefully, the immuno-oncology will bring about a paradigm shift of anti-cancer treatment for HCC.

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Section: Immune Checkpoint Blockades In Hccmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cancer immuotherapy for hepatocellular carcinoma

Lee¹,

Oh²,

Kim³

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…The tolerability of this class of agents greatly depends on the severity of immune‐related AEs (irAEs), although the majority of AEs are mild. Immune checkpoint inhibitors are an essential agent for immunotherapy; thus, we discuss the role of the immune checkpoint blockade in the treatment of HCC, including their combinations with other treatment methods …”

Section: Introductionmentioning

confidence: 99%

“…Immune checkpoint inhibitors are an essential agent for immunotherapy; thus, we discuss the role of the immune checkpoint blockade in the treatment of HCC, including their combinations with other treatment methods. [10][11][12]…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint blockade for the treatment of human hepatocellular carcinoma

Nishida

Kudo

2018

Hepatology Research

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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.

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“…Nishida et al [25] described the role of immune checkpoint blockade in the treatment for human HCC. They described that several immune checkpoints are involved in the suppression of an antitumor immune response.…”

mentioning

confidence: 99%

Role of Immune Checkpoint Blockade in the Treatment for Human Hepatocellular Carcinoma

Cited by 10 publications

References 32 publications

Cancer immuotherapy for hepatocellular carcinoma

Cancer immuotherapy for hepatocellular carcinoma

Immune checkpoint blockade for the treatment of human hepatocellular carcinoma

New Era of the Management of Liver Diseases and Liver Cancer: State-of-the-Art Progress in 2017

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