Mouse Models of Oncoimmunology in Hepatocellular Carcinoma

Bresnahan, Erin; Lindblad, Katherine E.; Lujambio, Amaia

doi:10.1158/1078-0432.ccr-19-2923

Cited by 14 publications

(12 citation statements)

References 89 publications

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“…Comprehensive reviews on mouse models of oncoimmunology in HCC have been conducted. 60 , 61 Despite programmed cell death protein 1 (PD1) immune checkpoint inhibitors have changed the landscape of cancer medicine and produced encouraging results in HCC, 62 , 63 not all patients resulted sensitive to anti-PD1 therapies indicating the onset of drug resistance mechanisms. Indeed, clinical responses are observed only in 20% of treated HCC patients.…”

Section: Immunotherapy-based Approaches In Hcc Animal Modelsmentioning

confidence: 99%

Animal Models of Hepatocellular Carcinoma: Current Applications in Clinical Research

Fornari¹,

Giovannini²,

Piscaglia³

et al. 2022

JHC

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In the last decade, relevant advances have occurred in the treatment of hepatocellular carcinoma (HCC), with novel drugs entering the clinical practice, among which tyrosine kinase inhibitors (TKIs) such as lenvatinib, cabozantinib and regorafenib, and immune checkpoint inhibitors (ICPIs) either alone or in combination with VEGF inhibitors. Clinical trials have driven the introduction of such novel molecules into the clinics but, at present, no biomarker drives the choice of first-line options, which relies only upon clinical and imaging assessment. Remarkably, clinical and imaging-based evaluations do not consider the huge heterogeneity of HCC and do not allow to realize the potential of personalized treatments. Preclinical research still does not inform the design of clinical trials, even though many animal models mimicking specific subgroups of HCC are available and might provide relevant information. Although animal models directly informing the clinical practice, such as patients-derived xenografts, are not used to help the choice of treatment in advanced HCC, however, the preclinical research can count on a wide range of valuable models. Here we will review some HCC models which might turn informative for specific questions in defined patient subgroups, and we will describe recent preclinical studies for the mechanistic evaluation of immunotherapy-based treatment approaches. To this aim, we will mainly focus on two issues: (i) HCC models informative on NAFLD-NASH HCC and (ii) HCC models helping to elucidate mechanisms underneath immunotherapy. We have chosen these two settings since they represent, respectively, the most rapidly arising cause of chronic liver disease (CLD) and HCC in western countries and the most promising therapeutic option for advanced HCC.

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Section: Immunotherapy-based Approaches In Hcc Animal Modelsmentioning

confidence: 99%

Animal Models of Hepatocellular Carcinoma: Current Applications in Clinical Research

Fornari¹,

Giovannini²,

Piscaglia³

et al. 2022

JHC

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“…Of particular interest are the implantable syngeneic mouse cancer models, which occupy a major position in tumor immunology and immunotherapy studies [132]. As compared to conventional xenografts, which require animal immunodeficiency, these models carry out the engraftment by subcutaneous or intravenous injection of mouse HCC cell lines or murine tumoral tissue in immunocompetent mice of the same genetic strain, while preserving the host immune system [132,133]. Reiberger and colleagues report the development of a syngeneic orthotopic HCC mouse model with CCl 4 -induced liver cirrhosis that mimics the features of human HCC [134].…”

Section: Xenograft Hcc Modelsmentioning

confidence: 99%

Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Blidișel

Marcovici

Coricovac

et al. 2021

Cancers

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Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

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“…To detect molecular and cellular predictors of positive response to immunotherapy, animal models are widely employed in preclinical investigations, particularly syngeneic, genetically engineered, and humanized mice [ 149 ]. All of them harbor certain advantages and disadvantages, which should be carefully considered to accurately address the respective questions concerning immunotherapy.…”

Section: Translational Studies To Overcome Resistance To Immunothementioning

confidence: 99%

Translational Considerations to Improve Response and Overcome Therapy Resistance in Immunotherapy for Hepatocellular Carcinoma

Heinrich

Castven

Galle

et al. 2020

Cancers

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Over the last decade, progress in systemic therapies significantly improved the outcome of primary liver cancer. More recently, precision oncological and immunotherapeutic approaches became the focus of intense scientific and clinical research. Herein, preclinical studies showed promising results with high response rates and improvement of overall survival. However, results of phase III clinical trials revealed that only a subfraction of hepatocellular carcinoma (HCC) patients respond to therapy and display only moderate objective response rates. Further, predictive molecular characteristics are largely missing. In consequence, suitable trial design has emerged as a crucial factor for the success of a novel compound. In addition, increasing knowledge from translational studies indicate the importance of targeting the tumor immune environment to overcome resistance to immunotherapy. Thus, combination of different immunotherapies with other treatment modalities including antibodies, tyrosine kinase inhibitors, or local therapies is highly promising. However, the mechanisms of failure to respond to immunotherapy in liver cancer are still not fully understood and the modulation of the immune system and cellular tumor composition is particularly relevant in this context. Altogether, it is increasingly clear that tailoring of immunotherapy and individualized approaches are required to improve efficacy and patient outcome in liver cancer. This review provides an overview of the current knowledge as well as translational considerations to overcome therapy resistance in immunotherapy of primary liver cancer.

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Mouse Models of Oncoimmunology in Hepatocellular Carcinoma

Cited by 14 publications

References 89 publications

Animal Models of Hepatocellular Carcinoma: Current Applications in Clinical Research

Animal Models of Hepatocellular Carcinoma: Current Applications in Clinical Research

Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Translational Considerations to Improve Response and Overcome Therapy Resistance in Immunotherapy for Hepatocellular Carcinoma

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