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Stromal and Immune Drivers of Hepatocarcinogenesis

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Book cover Hepatocellular Carcinoma

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

Abstract

In the large majority of cases, hepatocellular carcinoma (HCC) develops on the background of chronic liver inflammation and fibrosis. Liver microenvironment plays a crucial role in hepatocarcinogenesis, HCC progression, response to treatment, and patients’ long-term prognosis. Chronic liver inflammation and hepatocyte damage recruit and activate immune and stromal cells that release cytokines stimulating cell proliferation and producing liver fibrosis, hepatocellular stress, DNA damage, and chromosomal alterations that finally drive hepatocyte degeneration. Moreover, immune and stromal cells, e.g., cancer-associated fibroblasts, promote HCC progression by reducing tumor immunosurveillance, stimulating angiogenesis, and recruiting cancer stem cells. Activation of stromal and immune cells leads finally to epithelial–mesenchymal transition that confers increased initiation and metastasis of cancer cells and a greater resistance to therapies. Tumor microenvironment is also a relevant target for HCC treatment. Indeed, compounds targeting exhausted immune cells infiltrating HCC (i.e., nivolumab and pembrolizumab) have recently been shown to increase survival of HCC patients after sorafenib failure and were FDA-approved as a second-line treatment for advanced HCC.

* Antonio Saviano and Natascha Roehlen are co-first authors of this chapter

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Change history

  • 13 May 2020

    The book was inadvertently published with incorrect given name and family name in Chap. 4. The author name which is displayed as N.V. Violi is corrected to N. Vietti Violi.

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Authors and Affiliations

  1. Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Université de Strasbourg, Strasbourg, France

    Antonio Saviano, Natascha Roehlen, Alessia Virzì, Armando Andres Roca Suarez, Joachim Lupberger & Thomas F. Baumert

  2. Pôle Hépato-digestif, Institut Hopitalo-Universitaire, Hôpitaux Universitaires, Strasbourg, France

    Antonio Saviano & Thomas F. Baumert

  3. Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA

    Yujin Hoshida

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  1. Antonio Saviano
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    Yujin Hoshida

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Saviano, A. et al. (2019). Stromal and Immune Drivers of Hepatocarcinogenesis. In: Hoshida, Y. (eds) Hepatocellular Carcinoma. Molecular and Translational Medicine. Humana, Cham. https://doi.org/10.1007/978-3-030-21540-8_15

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