Immune-based therapies for hepatocellular carcinoma

Pinato, David J.; Guerra, Nadia; Murphy, Ronan A.; Mineo, Takashi; Mauri, Francesco; Mukherjee, Sujit; Thursz, Mark; Wong, Ching Ngar; Sharma, Rohini; Rimassa, Lorenza

doi:10.1038/s41388-020-1249-9

Cited by 158 publications

(133 citation statements)

References 172 publications

(184 reference statements)

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“…Immune checkpoint inhibitors constitute the most promising treatment for HCC in the future, especially PD-1 and PD-L1 inhibitors [ 1 , 2 ]. The goal of this immune checkpoint is to prevent the overstimulation of immune response.…”

Section: Immunotherapy In Hccmentioning

confidence: 99%

“…Tremelimumab and ipilimumab are antibodies against CTLA-4. T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte activation gene 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) or V-domain Ig Suppressor of T cell Activation (VISTA) are other immune checkpoints, with ongoing clinical trials to demonstrate their clinical efficacy and outcomes in patients with HCC [ 2 , 30 ]. Co-expression of multiple immune checkpoints has been associated with a severely exhausted T cell state, typical for CD8+ T cells in the tumour microenvironment.…”

Section: Immunotherapy In Hccmentioning

confidence: 99%

“…Recently, immunotherapies, mainly immune checkpoint inhibitors of the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway, have emerged as an encouraging antitumour strategy for HCC [ 1 , 2 ]. The combination of ablation and immunotherapy can be a promising therapeutic approach and a breakthrough in HCC treatment.…”

Section: Introductionmentioning

confidence: 99%

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Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma

Dumolard

Ghelfi

Roth

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide and its incidence is rising. Percutaneous locoregional therapies, such as radiofrequency ablation and microwave ablation, are widely used as curative treatment options for patients with small HCC, but their effectiveness remains restricted because of the associated high rate of recurrence, occurring in about 70% of patients at five years. These thermal ablation techniques have the particularity to induce immunomodulation by destroying tumours, although this is not sufficient to raise an effective antitumour immune response. Ablative therapies combined with immunotherapies could act synergistically to enhance antitumour immunity. This review aims to understand the different immune changes triggered by radiofrequency ablation and microwave ablation as well as the interest in using immunotherapies in combination with thermal ablation techniques as a tool for complementary immunomodulation.

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Section: Immunotherapy In Hccmentioning

confidence: 99%

Section: Immunotherapy In Hccmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma

Dumolard

Ghelfi

Roth

et al. 2020

IJMS

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“…Host immune surveillance is critical for the detection and removal of aberrant and/or transformed cells and requires an effective crosstalk between the innate and adaptive immune systems. However, in cases of advanced liver disease, especially in HCC patients, dysfunctional T cell phenotypes are well described, and immune checkpoint molecules such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are upregulated in HCC-infiltrating T lymphocytes [2,3]. CTLA-4 negatively modulates the priming phase of the T cell response by outcompeting CD28 for binding of its ligands CD80/86, which are found on the surface of antigen-presenting cells (APCs), resulting in inhibitory signaling.…”

Section: Liver Tolerance and Implication For Diseasesmentioning

confidence: 99%

“…Its ligand, PD-L1, is highly expressed in HCC, and the constitutive activation of this axis leads to T cell exhaustion. Other inhibitory immune checkpoint molecules found to be upregulated in HCC include T cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte-activation gene 3 (LAG-3) [3].…”

Section: Liver Tolerance and Implication For Diseasesmentioning

confidence: 99%

Chronic Viral Liver Diseases: Approaching the Liver Using T Cell Receptor-Mediated Gene Technologies

Healy

Pasetto

Sobkowiak

et al. 2020

Cells

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Chronic infection with viral hepatitis is a major risk factor for liver injury and hepatocellular carcinoma (HCC). One major contributing factor to the chronicity is the dysfunction of virus-specific T cell immunity. T cells engineered to express virus-specific T cell receptors (TCRs) may be a therapeutic option to improve host antiviral responses and have demonstrated clinical success against virus-associated tumours. This review aims to give an overview of TCRs identified from viral hepatitis research and discuss how translational lessons learned from cancer immunotherapy can be applied to the field. TCR isolation pipelines, liver homing signals, cell type options, as well as safety considerations will be discussed herein.

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Integrating bulk and single‐cell RNA sequencing reveals cellular heterogeneity and immune infiltration in hepatocellular carcinoma

et al. 2022

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Efficacy of immunotherapy in hepatocellular carcinoma (HCC) is blocked by its high degree of inter‐ and intra‐tumor heterogeneity and immunosuppressive tumor microenvironment. However, the correlation between tumor heterogeneity and immunosuppressive microenvironment in HCC has not been well addressed. Here, we endeavored to dissect inter‐ and intra‐tumor heterogeneity in HCC and uncover how they contribute to the immunosuppressive microenvironment. We performed consensus molecular subtyping with non‐negative matrix factorization (NMF) clustering to stratify the inter‐heterogeneity profile of HCC tumors. We grouped HCC tumors from the Cancer Genome Atlas (TCGA) patients into three subtypes (S1, S2 and S3), where S1 was characterized as a ‘hot tumor’ profile with high expression level of T cell genes and rate of immune scores. S2 was characterized as a ‘cold tumor’ profile with the highest tumor purity score, and S3 as an ‘immunosuppressed tumor’ profile with the poorest prognosis and a high expression level of immunosuppressive genes such as cytotoxic T‐lymphocyte‐associated protein‐4, TIGIT, and PDCD1 . Moreover, we combined weighted gene co‐expression network analysis and single‐cell regulatory network inference and clustering (SCENIC) in the single‐cell dataset of the S3‐like subtype (CS3) and identified a transcription factor, BATF , which could upregulate immunosuppressive genes. Finally, we identified a cell interaction network in which a myeloid‐derived suppressor cell‐like macrophage subtype could promote the formation of immunosuppressive T‐cells.

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Immune-based therapies for hepatocellular carcinoma

Cited by 158 publications

References 172 publications

Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma

Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma

Chronic Viral Liver Diseases: Approaching the Liver Using T Cell Receptor-Mediated Gene Technologies

Integrating bulk and single‐cell RNA sequencing reveals cellular heterogeneity and immune infiltration in hepatocellular carcinoma

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