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Cancers
Special Issues
Immunotherapy for Hepatocellular Carcinoma: Novel Experimental Approaches and Biomarkers
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Immunotherapy for Hepatocellular Carcinoma: Novel Experimental Approaches and Biomarkers

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

Deadline for manuscript submissions: 30 April 2024 | Viewed by 2784

Special Issue Editors

Dr. Albert Morales

E-Mail Website
Guest Editor
Department of Cell Death and Proliferation, IIBB-CSIC, IDIBAPS, 08036 Barcelona, Spain
Interests: cancer; oxidative stress; sphingolipids; liver disease
Dr. Montserrat Marí

E-Mail Website
Guest Editor
Department of Cell Death and Proliferation, Institut D'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (IIBB-CSIC), Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain
Interests: liver diseases; nafld; liver fibrosis; nkt cells; liver immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Hepatocellular carcinoma (HCC), the most common form of liver cancer, continues to be a serious medical problem with poor prognosis and increasing incidence. Fortunately, after a decade of sorafenib as the standard therapy for advanced HCC, several tyrosine kinase inhibitors (TKIs), antiangiogenic antibodies, and immune checkpoint inhibitors have found their way into the clinic. In particular, advances in immunotherapy are finally reaching HCC patients.

Although infections by hepatitis B virus and hepatitis C virus remain principal factors for HCC development, the rise of non-alcoholic steatohepatitis from diabetes mellitus or metabolic syndrome is impeding HCC decline. Knowledge of specific molecular mechanisms, based on the etiology and the HCC microenvironment that influence tumor growth and immune control, will be crucial in the coming years for deciding which drugs to prescribe.  

This Special Issue aims to find new experimental approaches to improve the efficacy of immunotherapy and provide innovative strategies in case of failure. Novel biomarkers are required to predict treatment efficacy or to identify specific patients for particular therapies. After the advent of immunotherapy for the treatment of HCC, animal models must be improved and molecular targets that alter the immune response must be tested, seeking to extend the success of therapy to non-responders. This Special Issue welcomes both original research articles and reviews based on these related topics.

Dr. Albert Morales
Dr. Montserrat Marí
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 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

  • immunotherapy
  • hepatocellular carcinoma
  • liver diseases
  • liver immunology
  • biomarkers

Published Papers (3 papers)

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Research

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16 pages, 4375 KiB  
Article
Induction of the Inflammasome Pathway by Tyrosine Kinase Inhibitors Provides an Actionable Therapeutic Target for Hepatocellular Carcinoma
by Anna Tutusaus, Marco Sanduzzi-Zamparelli, Loreto Boix, Patricia Rider, Silvia Subías, Pablo García de Frutos, Anna Colell, Montserrat Marí, María Reig and Albert Morales
Cancers 2024, 16(8), 1491; https://doi.org/10.3390/cancers16081491 - 13 Apr 2024
Viewed by 492
Abstract
During the last decade, tyrosine kinase inhibitors (TKIs) sorafenib and regorafenib have been standard systemic treatments for advanced hepatocellular carcinoma (HCC). Previous data associated sorafenib with inflammasome activation. However, the role of the inflammasome in sorafenib and regorafenib signaling has not been described [...] Read more.
During the last decade, tyrosine kinase inhibitors (TKIs) sorafenib and regorafenib have been standard systemic treatments for advanced hepatocellular carcinoma (HCC). Previous data associated sorafenib with inflammasome activation. However, the role of the inflammasome in sorafenib and regorafenib signaling has not been described in liver cancer patients. For this purpose, we analyzed inflammasome-related transcriptomic changes in a murine HCC model. Our data confirmed inflammasome activation after both TKI treatments, sharing a similar pattern of increased gene expression. According to human database results, transcriptional increase of inflammasome genes is associated with poorer prognosis for male liver cancer patients, suggesting a sex-dependent role for inflammasome activation in HCC therapy. In biopsies of HCC and its surrounding tissue, we detected durable increases in the inflammasome activation pattern after sorafenib or regorafenib treatment in male patients. Further supporting its involvement in sorafenib action, inflammasome inhibition (MCC950) enhanced sorafenib anticancer activity in experimental HCC models, while no direct in vitro effect was observed in HCC cell lines. Moreover, activated human THP-1 macrophages released IL-1β after sorafenib administration, while 3D Hep3B spheres displayed increased tumor growth after IL-1β addition, pointing to the liver microenvironment as a key player in inflammasome action. In summary, our results unveil the inflammasome pathway as an actionable target in sorafenib or regorafenib therapy and associate an inflammasome signature in HCC and surrounding tissue with TKI administration. Therefore, targeting inflammasome activation, principally in male patients, could help to overcome sorafenib or regorafenib resistance and enhance the efficacy of TKI treatments in HCC. Full article
(This article belongs to the Special Issue Immunotherapy for Hepatocellular Carcinoma: Novel Experimental Approaches and Biomarkers)
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18 pages, 6928 KiB  
Article
Peripheral T Cell Subpopulations as a Potential Surrogate Biomarker during Atezolizumab plus Bevacizumab Treatment for Hepatocellular Carcinoma
by Yuki Shirane, Yasutoshi Fujii, Atsushi Ono, Hikaru Nakahara, Clair Nelson Hayes, Ryoichi Miura, Serami Murakami, Naoya Sakamoto, Shinsuke Uchikawa, Hatsue Fujino, Takashi Nakahara, Eisuke Murakami, Masami Yamauchi, Daiki Miki, Tomokazu Kawaoka, Koji Arihiro, Masataka Tsuge and Shiro Oka
Cancers 2024, 16(7), 1328; https://doi.org/10.3390/cancers16071328 - 28 Mar 2024
Viewed by 572
Abstract
The therapeutic benefits of the immunotherapeutic combination of atezolizumab and bevacizumab (Atez/Bev) in hepatocellular carcinoma (HCC) vary. Therapeutic biomarkers might help improve outcomes for HCC patients receiving Atez/Bev therapy. The role of systemic immune profiles in HCC progression also remains unclear. This study [...] Read more.
The therapeutic benefits of the immunotherapeutic combination of atezolizumab and bevacizumab (Atez/Bev) in hepatocellular carcinoma (HCC) vary. Therapeutic biomarkers might help improve outcomes for HCC patients receiving Atez/Bev therapy. The role of systemic immune profiles in HCC progression also remains unclear. This study aimed to evaluate the status and dynamics of peripheral T cell subpopulations in HCC patients receiving Atez/Bev treatment and to explore biomarkers predictive of a therapeutic response. We enrolled 83 unresectable advanced HCC patients who commenced Atez/Bev treatment at our hospital between October 2020 and June 2022. Peripheral T cell subpopulations in peripheral blood mononuclear cells at baseline and 3 weeks post-treatment were investigated using flow cytometry and compared with those in control samples from 18 healthy individuals. We retrospectively analyzed the association between peripheral T cell subpopulation profiles and clinical outcomes. Baseline peripheral T cell subpopulations could be profiled in 70 patients with sufficient cell counts, among whom 3-week subpopulations could be evaluated in 51 patients. Multivariate analysis showed that a high baseline proportion of CD8+ central memory T (TCM) cells was independently associated with longer progression-free survival (PFS). Further, overall survival (OS) was significantly prolonged in patients with increased CD8+ effector memory T (TEM) cell proportions. In conclusion, TCM proportion at baseline might be a good indicator of the efficacy of Atez/Bev therapy. Furthermore, observation of increasing TEM proportions might be an early predictor of the potential clinical benefits of treatment. Full article
(This article belongs to the Special Issue Immunotherapy for Hepatocellular Carcinoma: Novel Experimental Approaches and Biomarkers)
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Review

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20 pages, 355 KiB  
Review
Targeting the Heterogeneous Tumour-Associated Macrophages in Hepatocellular Carcinoma
by Aloña Agirre-Lizaso, Maider Huici-Izagirre, Josu Urretabizkaia-Garmendia, Pedro M. Rodrigues, Jesus M. Banales and Maria J. Perugorria
Cancers 2023, 15(20), 4977; https://doi.org/10.3390/cancers15204977 - 13 Oct 2023
Viewed by 1198
Abstract
Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that comprises a complex tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are one of the most abundant immune cells present in the TME, and play a key role both in the development and in the [...] Read more.
Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that comprises a complex tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are one of the most abundant immune cells present in the TME, and play a key role both in the development and in the progression of HCC. Thus, TAM-based immunotherapy has been presented as a promising strategy to complement the currently available therapies for HCC treatment. Among the novel approaches focusing on TAMs, reprogramming their functional state has emerged as a promising option for targeting TAMs as an immunotherapy in combination with the currently available treatment options. Nevertheless, a further understanding of the immunobiology of TAMs is still required. This review synthesizes current insights into the heterogeneous nature of TAMs in HCC and describes the mechanisms behind their pro-tumoural polarization focusing the attention on their interaction with HCC cells. Furthermore, this review underscores the potential involvement of TAMs’ reprogramming in HCC therapy and highlights the urgency of advancing our understanding of these cells within the dynamic landscape of HCC. Full article
(This article belongs to the Special Issue Immunotherapy for Hepatocellular Carcinoma: Novel Experimental Approaches and Biomarkers)
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