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Tumor Immune Microenvironment and Immunotherapy: Novel Insights and Future Perspectives...
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Tumor Immune Microenvironment and Immunotherapy: Novel Insights and Future Perspectives in HCC

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 3708

Special Issue Editor

Dr. Daniela Cornelia Lazăr

E-Mail Website
Guest Editor
Department V of Internal Medicine I, Discipline of Internal Medicine IV, “Victor Babeș” University of Medicine and Pharmacy Timișoara, Eftimie Murgu Sq. No. 2, 300041 Timișoara, Romania
Interests: digestive oncology; gastric cancer; hepatocellular carcinoma; immunotherapy; tumor angiogenesis; inflammatory bowel diseases

Special Issue Information

Dear Colleagues,

Hepatocellular carcinoma (HCC), the most common histological subtype of liver cancer, represents one of the leading causes of cancer-related deaths worldwide, showing a rising incidence and mortality in recent decades due to the high prevalence of chronic hepatitis and liver cirrhosis. Despite recent advances in surgical techniques (laparoscopic tumor resections, extension of indications, and types of liver transplantation), interventional procedures for locally advanced tumors and chemotherapy strategies for metastatic disease, including development of novel therapies, such as molecular targeted agents (MTA), the prognosis of this cancer remains worse due to frequent relapses and metastasis.

Recently, numerous immunotherapeutic strategies have been elaborated in order to improve the therapeutic efficacy in many cancers, including treatments using immune checkpoint inhibitors (ICI) and monoclonal antibodies, cytokines or cytotoxic cells, gene transferred vaccines, and many others, with the aim to enhance the host capacity to fight against the tumor or to increase the sensitivity of tumor cells to the treatment. In this regard, the therapeutic algorithm of HCC changed radically and prognosis of patients with HCC has improved by introduction of modern immunotherapy, nowadays the combination of an immune checkpoint inhibitor (ICI) plus a VEGF inhibitor being regarded as the first line of treatment in advanced stages of HCC.

This Special Issue focuses on the latest research trying to elucidate the complex interaction between the host immune microenvironment and hepatocellular cancer development and progression, with further identification of prognostic immune markers and biomarkers that predict treatment response. Moreover, this fundamental insight of the dynamic process of oncogenesis will lead to the development of new treatments targeted on blocking the signals of immunosuppression induced by tumor cells or on enhancing the host immune response by modulating the tumor immune micro-environment. Both preclinical research and clinical studies using biomolecular experiments are welcomed for this Special Issue.

Dr. Daniela Cornelia Lazăr
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • tumor immune microenvironment
  • immunotherapy
  • hepatocellular carcinoma
  • prognostic immune markers
  • biomarkers for treatment response
  • drug discovery

Published Papers (2 papers)

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Research

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17 pages, 3288 KiB  
Article
Alterations in Hepatocellular Carcinoma-Specific Immune Responses Following Hepatitis C Virus Elimination by Direct-Acting Antivirals
by Shihui Li, Eishiro Mizukoshi, Kazunori Kawaguchi, Miyabi Miura, Michiko Nishino, Tetsuro Shimakami, Kuniaki Arai, Taro Yamashita, Yoshio Sakai, Tatsuya Yamashita, Masao Honda and Shuichi Kaneko
Int. J. Mol. Sci. 2022, 23(19), 11623; https://doi.org/10.3390/ijms231911623 - 1 Oct 2022
Cited by 2 | Viewed by 1656
Abstract
Direct-acting antivirals (DAAs) have recently revolutionized the eradication of chronic hepatitis C virus (HCV) infection. However, the effects of DAAs on the development of hepatocellular carcinoma (HCC) remain unknown. Therefore, the present study aimed to investigate immune responses to HCC influenced by DAAs [...] Read more.
Direct-acting antivirals (DAAs) have recently revolutionized the eradication of chronic hepatitis C virus (HCV) infection. However, the effects of DAAs on the development of hepatocellular carcinoma (HCC) remain unknown. Therefore, the present study aimed to investigate immune responses to HCC influenced by DAAs in HCV-infected patients and elucidate the underlying mechanisms. We compared immune responses to 19 different HCC-related tumor-associated antigen (TAA)-derived peptides and host immune cell profiles before and 24 weeks after a treatment with DAAs in 47 HLA-A24-positive patients. The relationships between the different immune responses and phenotypic changes in immune cells were also examined. The treatment with DAAs induced four types of immune responses to TAAs and markedly altered host immune cell profiles. Prominently, reductions in the frequencies of PD-1+CD4+ and PD-1+CD8+ T cells by DAAs were associated with enhanced immune responses to TAAs. The HCV F protein was identified as contributing to the increased frequency of PD-1+ T cells, which may be decreased after eradication by DAAs. DAAs altered the immune responses of patients to HCC by decreasing the frequency of PD-1-expressing CD4+ and CD8+ T cells. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment and Immunotherapy: Novel Insights and Future Perspectives in HCC)
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Review

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16 pages, 3772 KiB  
Review
Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs
by Qingqing Liu, Xiaoyu Yan, Runyuan Li, Yuan Yuan, Jian Wang, Yuanxin Zhao, Jiaying Fu and Jing Su
Int. J. Mol. Sci. 2024, 25(2), 996; https://doi.org/10.3390/ijms25020996 - 13 Jan 2024
Viewed by 1648
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and, with increasing research on the tumor immune microenvironment (TIME), the immunosuppressive micro-environment of HCC hampers further application of immunotherapy, even though immunotherapy can provide survival benefits to patients with advanced liver cancer. [...] Read more.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and, with increasing research on the tumor immune microenvironment (TIME), the immunosuppressive micro-environment of HCC hampers further application of immunotherapy, even though immunotherapy can provide survival benefits to patients with advanced liver cancer. Current studies suggest that polyamine metabolism is not only a key metabolic pathway for the formation of immunosuppressive phenotypes in tumor-associated macrophages (TAMs), but it is also profoundly involved in mitochondrial quality control signaling and the energy metabolism regulation process, so it is particularly important to further investigate the role of polyamine metabolism in the tumor microenvironment (TME). In this review, by summarizing the current research progress of key enzymes and substrates of the polyamine metabolic pathway in regulating TAMs and T cells, we propose that polyamine biosynthesis can intervene in the process of mitochondrial energy metabolism by affecting mitochondrial autophagy, which, in turn, regulates macrophage polarization and T cell differentiation. Polyamine metabolism may be a key target for the interactive dialog between HCC cells and immune cells such as TAMs, so interfering with polyamine metabolism may become an important entry point to break intercellular communication, providing new research space for developing polyamine metabolism-based therapy for HCC. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment and Immunotherapy: Novel Insights and Future Perspectives in HCC)
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