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The Biology of Hepatocellular Carcinoma: Implications for Genomic and Immune...
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The Biology of Hepatocellular Carcinoma: Implications for Genomic and Immune Therapies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 8846

Special Issue Editor

Prof. Dr. Naoshi Nishida

E-Mail Website
Guest Editor
Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan
Interests: hepatocellular carcinoma; molecular classification; tumor microenvironment; genome; epigenome; transcriptome; diagnosis; treatment; molecular targeted agent; multikinase inhibitor; immune checkpoint inhibitor; artificial intelligence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high recurrence rate and mortality. Although the biological behavior of HCC is complex, where a variety of oncogenic pathways is involved, recent analyses of genome, epigenome, and transcriptome indicate a sophisticated molecular classification of this type of cancer that reflect HCC biology. Such “omics” analyses allow us to show a responsible cancer pathway and help to develop specific molecular targeted agents as well as understand cancer biology in each case. In addition, it is known that omics-based classifications are also associated with the immune phenotype of HCC, which should affect the efficacy of immune-based treatment, including immune checkpoint inhibitors in addition to molecular targeted agents. From these points of view, understanding biology in each HCC is required to establish the personalized medicine expected for the effective treatment of cancer.

From this point of view, this Special Issue will highlight the current state of the art in genetic and immune therapies based on the biological understanding of HCC from both basic and clinical aspects.

In addition, recent technology in artificial intelligence (AI) is playing a critical role in applying omics data on understanding the biology in each HCC; AI-based analyses of precision medicine are also welcome.

Prof. Dr. Naoshi Nishida
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hepatocellular carcinoma
  • diagnosis
  • treatment
  • molecular targeted agent
  • immune checkpoint inhibitor
  • artificial intelligence

Published Papers (3 papers)

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Review

15 pages, 1102 KiB  
Review
Role of β-Catenin Activation in the Tumor Immune Microenvironment and Immunotherapy of Hepatocellular Carcinoma
by Masahiro Morita, Naoshi Nishida, Tomoko Aoki, Hirokazu Chishina, Masahiro Takita, Hiroshi Ida, Satoru Hagiwara, Yasunori Minami, Kazuomi Ueshima and Masatoshi Kudo
Cancers 2023, 15(8), 2311; https://doi.org/10.3390/cancers15082311 - 15 Apr 2023
Cited by 9 | Viewed by 2490
Abstract
Recently, the therapeutic combination of atezolizumab and bevacizumab was widely used to treat advanced hepatocellular carcinoma (HCC). According to recent clinical trials, immune checkpoint inhibitors (ICIs) and molecular target agents are expected to be key therapeutic strategies in the future. Nonetheless, the mechanisms [...] Read more.
Recently, the therapeutic combination of atezolizumab and bevacizumab was widely used to treat advanced hepatocellular carcinoma (HCC). According to recent clinical trials, immune checkpoint inhibitors (ICIs) and molecular target agents are expected to be key therapeutic strategies in the future. Nonetheless, the mechanisms underlying molecular immune responses and immune evasion remain unclear. The tumor immune microenvironment plays a vital role in HCC progression. The infiltration of CD8-positive cells into tumors and the expression of immune checkpoint molecules are key factors in this immune microenvironment. Specifically, Wnt/β catenin pathway activation causes “immune exclusion”, associated with poor infiltration of CD8-positive cells. Some clinical studies suggested an association between ICI resistance and β-catenin activation in HCC. Additionally, several subclassifications of the tumor immune microenvironment were proposed. The HCC immune microenvironment can be broadly divided into inflamed class and non-inflamed class, with several subclasses. β-catenin mutations are important factors in immune subclasses; this may be useful when considering therapeutic strategies as β-catenin activation may serve as a biomarker for ICI. Various types of β-catenin modulators were developed. Several kinases may also be involved in the β-catenin pathway. Therefore, combinations of β-catenin modulators, kinase inhibitors, and ICIs may exert synergistic effects. Full article
(This article belongs to the Special Issue The Biology of Hepatocellular Carcinoma: Implications for Genomic and Immune Therapies)
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14 pages, 1354 KiB  
Review
Advances in Immunotherapy for Hepatocellular Carcinoma
by Satoru Hagiwara, Naoshi Nishida and Masatoshi Kudo
Cancers 2023, 15(7), 2070; https://doi.org/10.3390/cancers15072070 - 30 Mar 2023
Cited by 4 | Viewed by 2321
Abstract
Immune checkpoint inhibitors (ICIs) aim to induce immune responses against tumors and are less likely to develop drug resistance than molecularly targeted drugs. In addition, they are characterized by a long-lasting antitumor effect. However, since its effectiveness depends on the tumor’s immune environment, [...] Read more.
Immune checkpoint inhibitors (ICIs) aim to induce immune responses against tumors and are less likely to develop drug resistance than molecularly targeted drugs. In addition, they are characterized by a long-lasting antitumor effect. However, since its effectiveness depends on the tumor’s immune environment, it is essential to understand the immune environment of hepatocellular carcinoma to select ICI therapeutic indications and develop biomarkers. A network of diverse cellular and humoral factors establishes cancer immunity. By analyzing individual cases and classifying them from the viewpoint of tumor immunity, attempts have been made to select the optimal therapeutic drug for immunotherapy, including ICIs. ICI treatment is discussed from the viewpoints of immune subclass of HCC, Wnt/β-catenin mutation, immunotherapy in NASH-related HCC, the mechanism of HPD onset, and HBV reactivation. Full article
(This article belongs to the Special Issue The Biology of Hepatocellular Carcinoma: Implications for Genomic and Immune Therapies)
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Figure 1

15 pages, 1442 KiB  
Review
Clinical Significance of the Duality of Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma
by Tomoko Aoki, Naoshi Nishida and Masatoshi Kudo
Cancers 2022, 14(2), 444; https://doi.org/10.3390/cancers14020444 - 17 Jan 2022
Cited by 22 | Viewed by 3560
Abstract
Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors has been approved as a first-line treatment for unresectable hepatocellular carcinoma (HCC), indicating a critical role of ICIs in the treatment of HCC. However, 20% of patients do not respond [...] Read more.
Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors has been approved as a first-line treatment for unresectable hepatocellular carcinoma (HCC), indicating a critical role of ICIs in the treatment of HCC. However, 20% of patients do not respond effectively to ICIs; mutations in the activation of the Wnt/β-catenin pathway are known to contribute to primary resistance to ICIs. From this point of view, non-invasive detection of Wnt/β-catenin activation should be informative for the management of advanced HCC. Wnt/β-catenin mutations in HCC have a dual aspect, which results in two distinct tumor phenotypes. HCC with minimal vascular invasion, metastasis, and good prognosis is named the “Jekyll phenotype”, while the poorly differentiated HCC subset with frequent vascular invasion and metastasis, cancer stem cell features, and high serum Alpha fetoprotein levels, is named the “Hyde phenotype”. To differentiate these two HCC phenotypes, a combination of the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging and fluoro-2-deoxy-D-glucose-PET/CT may be useful. The former is applicable for the detection of the Jekyll phenotype, as nodules present higher enhancement on the hepatobiliary phase, while the latter is likely to be informative for the detection of the Hyde phenotype by showing an increased glucose uptake. Full article
(This article belongs to the Special Issue The Biology of Hepatocellular Carcinoma: Implications for Genomic and Immune Therapies)
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