Special Issue "Immunotherapy in Hepatocellular Carcinoma"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 30 June 2020.

Special Issue Editors

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; diagnosis; cancer treatment; molecular carcinogenesis; genetics; epigenetics; tumor suppressor gene; data base; artificial intelligence; bioinformatics
Prof. Dr. Masatoshi Kudo
E-Mail Website
Guest Editor
Department of Gastroenterology and Hepatology, Kindai University, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan.
Interests: nodule-in-nodule HCC; Coded phase inversion harmonic; Pure arterial phase imaging; dysplastic nodule; nodule-in-nodule; Sonazoid

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with a high recurrence rate and mortality, especially for patients with advanced stages of the disease. Recent advancements of molecular targeted therapy—such as targeting VEGFR, FGFR, PDGFR, RAF, and MET—have led to improvements in the survival of such patients. However, a variety of genetic and epigenetic changes emerging in HCC cells should result in the acquisition of resistance to molecular targeted therapies.

On the other hand, restoring acquired immunity to HCC should suppress the progression of this type of tumor even in patients who progress on molecular targeted therapies. For example, recent clinical trials showed that immune checkpoint inhibitors are effective regardless of the response to prior therapies, including tyrosine kinase inhibitors, and a durable response was also observed. More importantly, a combination of immune checkpoint inhibitors with molecular targeted therapy, reportedly cause a strong anti-tumor response in HCC. The U.S. Food and Drug Administration granted a breakthrough therapy designation to the atezolizumab (anti-PD-L1 antibody)/bevacizumab (anti-VEGF-A antibody) combination as the first-line treatment for patients with advanced HCC. Although many HCC patients still remain refractory to the monotherapy of immune checkpoint inhibitors, several other trials that target immune suppressive cells and molecules—including stromal cells, humoral mediators, and suppressive checkpoint molecules—are ongoing, suggesting the rapid advancement of immunotherapy in the field of HCC treatment in the near future.

Based on this evidence, a deep understanding of the immunological status and biological targets modulating immunological microenvironments should be quite informative for the development of future immunotherapy in HCC. From this point of view, this Special Issue will highlight the current state of the art in the immunotherapy of HCC from both the basic and clinical perspectives, and outline future perspectives for improving therapies.

Dr. Naoshi Nishida
Prof. Dr. Masatoshi Kudo
Guest Editors

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 papers will be 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 monthly 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 1800 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
  • immunotherapy
  • immuno-oncology
  • immune checkpoint inhibitors
  • clinical trial

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Etiology-Specific Analysis of Hepatocellular Carcinoma Transcriptome Reveals Genetic Dysregulation in Pathways Implicated in Immunotherapy Efficacy
Cancers 2019, 11(9), 1273; https://doi.org/10.3390/cancers11091273 - 30 Aug 2019
Abstract
Immunotherapy has emerged in recent years as arguably the most effective treatment for advanced hepatocellular carcinoma (HCC), but the failure of a large percentage of patients to respond to immunotherapy remains as the ultimate obstacle to successful treatment. Etiology-associated dysregulation of immune-associated (IA) [...] Read more.
Immunotherapy has emerged in recent years as arguably the most effective treatment for advanced hepatocellular carcinoma (HCC), but the failure of a large percentage of patients to respond to immunotherapy remains as the ultimate obstacle to successful treatment. Etiology-associated dysregulation of immune-associated (IA) genes may be central to the development of this differential clinical response. We identified immune-associated genes potentially dysregulated by alcohol or viral hepatitis B in HCC and validated alcohol-induced dysregulations in vitro while using large-scale RNA-sequencing data from The Cancer Genome Atlas (TCGA). Thirty-four clinically relevant dysregulated IA genes were identified. We profiled the correlation of all genomic alterations in HCC patients to IA gene expression while using the information theory-based algorithm REVEALER to investigate the molecular mechanism for their dysregulation and explore the possibility of genome-based patient stratification. We also studied gene expression regulators and identified multiple microRNAs that were implicated in HCC pathogenesis that can potentially regulate these IA genes’ expression. Our study identified potential key pathways, including the IL-7 signaling pathway and TNFRSF4 (OX40)- NF-κB pathway, to target in immunotherapy treatments and presents microRNAs as promising therapeutic targets for dysregulated IA genes because of their extensive regulatory roles in the cancer immune landscape. Full article
(This article belongs to the Special Issue Immunotherapy in Hepatocellular Carcinoma)
Show Figures

Figure 1

Review

Jump to: Research

Open AccessFeature PaperReview
Rationale of Immunotherapy in Hepatocellular Carcinoma and Its Potential Biomarkers
Cancers 2019, 11(12), 1926; https://doi.org/10.3390/cancers11121926 - 03 Dec 2019
Abstract
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is derived mostly from a background of chronic inflammation. Multiple immunotherapeutic strategies have been evaluated in HCC, with some degree of success, particularly with immune checkpoint blockade (ICB). Despite the initial enthusiasm, treatment [...] Read more.
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is derived mostly from a background of chronic inflammation. Multiple immunotherapeutic strategies have been evaluated in HCC, with some degree of success, particularly with immune checkpoint blockade (ICB). Despite the initial enthusiasm, treatment benefit is only appreciated in a modest proportion of patients (response rate to single agent ~20%). Therapy-induced immune-related adverse events (irAEs) and economic impact are pertinent considerations with ICB. It is imperative that a deeper understanding of its mechanisms of action either as monotherapy or in combination with other therapeutic agents is needed. We herein discuss the latest developments in the immunotherapeutic approaches for HCC, the potential predictive biomarkers., and the rationale for combination therapies. We also outline promising future immunotherapeutic strategies for HCC patients. Full article
(This article belongs to the Special Issue Immunotherapy in Hepatocellular Carcinoma)
Open AccessReview
Overview of Immune Checkpoint Inhibitors Therapy for Hepatocellular Carcinoma, and The ITA.LI.CA Cohort Derived Estimate of Amenability Rate to Immune Checkpoint Inhibitors in Clinical Practice
Cancers 2019, 11(11), 1689; https://doi.org/10.3390/cancers11111689 - 30 Oct 2019
Abstract
Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment where it arises—advanced chronic liver disease—to its heterogeneous clinical and biological behaviour. The advent, and good results, of [...] Read more.
Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment where it arises—advanced chronic liver disease—to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC. According to this background, initial studies with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) antibody, showed promising results, and further studies exploring the effects of other immune checkpoint inhibitors, alone or with other drugs, are currently underway. However, we are still far from the identification of the correct setting, and sequence, where these drugs might be used in clinical practice, and their actual applicability in real-life is unknown. This review focuses on HCC immunobiology and on the potential of immune checkpoint blockade therapy for this tumour, with a critical evaluation of the available trials on immune checkpoint blocking antibodies treatment for HCC. Moreover, it assesses the potential applicability of immune checkpoint inhibitors in the real-life setting, by analysing a large, multicentre cohort of Italian patients with HCC. Full article
(This article belongs to the Special Issue Immunotherapy in Hepatocellular Carcinoma)
Show Figures

Figure 1

Open AccessReview
Predictive Factors for Response to PD-1/PD-L1 Checkpoint Inhibition in the Field of Hepatocellular Carcinoma: Current Status and Challenges
Cancers 2019, 11(10), 1554; https://doi.org/10.3390/cancers11101554 - 14 Oct 2019
Abstract
Immunotherapies targeting immune checkpoints are fast-developing therapeutic approaches adopted for several tumor types that trigger unprecedented rates of durable clinical responses. Immune checkpoint programmed cell death protein 1 (PD-1), expressed primarily by T cells, and programmed cell death ligand 1 (PD-L1), expressed mainly [...] Read more.
Immunotherapies targeting immune checkpoints are fast-developing therapeutic approaches adopted for several tumor types that trigger unprecedented rates of durable clinical responses. Immune checkpoint programmed cell death protein 1 (PD-1), expressed primarily by T cells, and programmed cell death ligand 1 (PD-L1), expressed mainly by tumor cells, macrophages, and dendritic cells, are molecules that impede immune function, thereby allowing tumor cells to proliferate, grow and spread. PD-1/PD-L1 checkpoint inhibitors have emerged as a promising treatment strategy of hepatocellular carcinoma (HCC). However, only a minority of HCC patients benefit from this therapy. To find a niche for immune checkpoint inhibition in HCC patients, future strategies might require predictive factor-based patient selection, to identify patients who are likely to respond to the said therapy and combination strategies in order to enhance anti-tumor efficacy and clinical success. This review provides an overview of the most recent data pertaining to predictive factors for response to PD-1/PD-L1 checkpoint inhibition in the field of HCC. Full article
(This article belongs to the Special Issue Immunotherapy in Hepatocellular Carcinoma)
Show Figures

Figure 1

Back to TopTop