Current progress and prospect of immune checkpoint inhibitors in hepatocellular carcinoma (Review)

Zeng, Zhu; Yang, Baoqi; Liao, Zhengyin

doi:10.3892/ol.2020.11909

Cited by 11 publications

(41 citation statements)

References 88 publications

(166 reference statements)

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“… 48 The overexpression of CTLA-4 in HCC leads to uncontrolled growth of the tumors. 49 In recent years, increasing attention has been given to the role of immune regulation in tumors. From the results of Spearman correlation analysis between AURKA/AURKB and immunoinhibitors of HCC, AURKB might have a synergistic effect on the immunosuppression of T lymphocytes in the liver immune environment, which promotes the progression of the tumor.…”

Section: Discussionmentioning

confidence: 99%

AURKB as a Promising Prognostic Biomarker in Hepatocellular Carcinoma

Xiao

Zhang

2021

Evol Bioinform Online

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The Aurora kinases form a family of 3 genes encoding serine/threonine kinases and are involved in the regulation of cell division during the mitosis. This study was designed to investigate the prognostic role of Aurora kinases in hepatocellular carcinoma (HCC). In this study, we analyzed the expression, overall survival (OS) data, promoter methylation level, and relationship with immunoinhibitors of Aurora kinases in patients with HCC from GEPIA2, UALCAN, OncoLnc, and TISIDB databases. Protein-protein interaction (PPI) network, gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analysis were performed using the STRING database and Cytoscape software. We found that the mRNA expression, stages of HCC, and OS of AURKA and AURKB in HCC tissues were significantly different from control tissues, but there were significant inconsistencies in promoter methylation level and relationship with immunoinhibitors for AURKA and AURKB. None of the above items were significantly different for AURKC. Furthermore, a hub module including AURKA, AURKB, and AURKC was identified within the PPI network constructed with the Molecular Complex Detection (MCODE) plug-in in Cytoscape software. Our results show that AURKB could be a potential biomarker for HCC prognosis.

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Section: Discussionmentioning

confidence: 99%

AURKB as a Promising Prognostic Biomarker in Hepatocellular Carcinoma

Xiao

Zhang

2021

Evol Bioinform Online

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“…One of the possibilities as to why both the CheckMate 459 and the KEYNOTE‐240 trials did not reach their clinically predefined primary outcome endpoints was due to the fact that both trials were unable to account for the regulatory approval of the use of other second‐line targeted therapies for the treatment of advanced HCC, including Regorafenib (a multi‐target tyrosine kinase inhibitor) which was licensed for use by the FDA in 2017, whilst both clinical trials were still ongoing 42,46,49,51,56 . However, certain patient subgroups may have benefited from anti‐PD‐1 therapy more than others 51,56 .…”

Section: Patient Selection For Ici Monotherapiesmentioning

confidence: 99%

“…However, results from both the CheckMate 040 and KEYNOTE‐224 trials demonstrated non‐statistically significant associations between the levels of expression of PD‐L1 and survival outcomes 50,53 . Further research into characterising a potential role for PD‐L1 expression and establishing other molecular biomarkers in predicting a treatment response for ICIs in HCC is warranted 42,43,46‐49 …”

Section: Patient Selection For Ici Monotherapiesmentioning

confidence: 99%

Immunotherapies for hepatocellular carcinoma

et al. 2021

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Cases of hepatocellular carcinoma (HCC) are rapidly rising. This is particularly the case in the Western world, as a result of increasing rates of chronic liver disease, secondary to lifestyle‐associated risk factors and the lack of an established screening programme for the general population. Traditionally, radical/curative treatment options for HCC, including liver transplantation and surgical resection are reserved for the minority of patients, presenting with an early stage cancer. For patients with advanced disease, Sorafenib and Lenvatinib were, until recently, the only licensed systemic treatments, and provided only limited survival benefits at the cost of a multitude of potential side effects. Recent scientific advances in the field of cancer immunotherapy have renewed significant interest in advanced HCC, in order to fulfil this apparent area of unmet clinical need. This has led to the success and recent regulatory approval of an Atezolizumab/Bevacizumab combination for the first‐line treatment of advanced HCC following results from the IMbrave150 clinical trial in 2019, with further immune checkpoint inhibitors currently undergoing testing in advanced clinical trials. Furthermore, other cancer immunotherapies, including chimeric antigen receptor T‐cells, dendritic cell vaccines and oncolytic viruses are also in early stage clinical trials, for the treatment of advanced HCC. This review will summarise the major approaches that have been and are currently in development for the systemic treatment of advanced HCC, their advantages, drawbacks, and predictions of where this revolutionary treatment field will continue to travel for the foreseeable future.

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“…an ideal response for HCC patients. However, ICBs still represent a novel therapeutic advancement for HCC patients, especially for those with advanced disease (22). Numerous studies have shown that immune infiltration, which is a signature of tumor heterogeneity and the TME, showed a better response to ICBs.…”

Section: Low Expressionmentioning

confidence: 99%

CXCL5/CXCL8 is a promising potential prognostic and tumor microenvironment-related cluster in hepatocellular carcinoma

Jun¹,

Zhou²,

Wang³

et al. 2020

J Gastrointest Oncol

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Background: Immune checkpoint blockers (ICBs) are increasingly applied to treat patients with advanced HCC. However, the overall survival (OS) of HCC patients is still unsatisfactory, and there is no confirmed immune-related and prognostic gene to identify patients who could clinically benefit from this treatment.The tumor microenvironment (TME) is known to be closely related to immunotherapy and plays a pivotal role in the recurrence and progression of HCC. Our aim is to explore TME-related genes and identify the prognostic value in HCC patients. Methods: ESTIMATE, immune, and stromal scores were calculated for HCC patients based on RNA expression data from The Cancer Genome Atlas database. Differential expression analysis was performed to screen the differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was constructed to identify the key DEGs. Univariate and multivariate Cox analyses were adopted to validate hub DEGs associated with clinical prognosis, and a single-sample gene set enrichment analysis (ssGSEA) algorithm was used to dissect the landscape of tumor-infiltrating cells (TIC) in HCC. Finally, the relationship between hub immune-related genes and TIC was explored through difference and correlation analyses. Results: ESTIMATE, immune and stromal scores were all found to be associated with the OS of patients (P<0.05). A total of 1,112 DEGs were identified by comparing low and high score groups of immune and stromal scores. Most of DEGs were enriched in immune-related gene sets by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, the top 34 genes were included in the protein-protein interaction (PPI) network, and univariate Cox analysis focus on a novel prognosisrelated gene cluster CXCL5/CXCL8 (P<0.001). Regarding the immune landscape of HCC, univariable Cox regression analysis showed six immune cells to be associated with OS. Finally, 21 immune cells were commonly determined between high and low expression of CXCL5/CXCL8 , suggesting there is a close relationship between expression of CXCL5 and CXCL8 . Conclusions: Our study has revealed that the immune-related gene cluster of CXCL5 /CXCL8 could be ^ ORCID: Jun Zhu,

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Current progress and prospect of immune checkpoint inhibitors in hepatocellular carcinoma (Review)

Cited by 11 publications

References 88 publications

AURKB as a Promising Prognostic Biomarker in Hepatocellular Carcinoma

AURKB as a Promising Prognostic Biomarker in Hepatocellular Carcinoma

Immunotherapies for hepatocellular carcinoma

CXCL5/CXCL8 is a promising potential prognostic and tumor microenvironment-related cluster in hepatocellular carcinoma

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