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Cellular and molecular targets for the immunotherapy of hepatocellular carcinoma

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Abstract

Liver cancer is the sixth most common cancer worldwide and 3rd most common cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancer and is a major public health problem. Due to the advanced stages of HCC at the time of diagnosis, utilizing the conventional treatment for solid tumors frequently ends with treatment failure, recurrence, or poor survival. HCC is highly refractory to chemotherapy and other systemic treatments, and locoregional therapies or selective internal radiation therapies are largely palliative. Considering how the pathogenesis of HCC often induces an immunosuppressed state which is further amplified by post-treatment recurrence and reactivation, immunostimulation provides a potential novel approach for the treatment of HCC. Immune response(s) of the body may be potentiated by immunomodulation of various effector cells such as B-cells, T-cells, Treg cells, natural killer cells, dendritic cells, cytotoxic T-lymphocytes, and other antigen-presenting cells; cellular components such as genes and microRNA; and molecules such as proteins, proteoglycans, surface receptors, chemokines, and cytokines. Targeting these effectors individually has helped in the development of newer therapeutic approaches; however, combinational therapies targeting multi-faceted biomarkers have yielded better results. Still, there is a need for further research to develop novel therapeutic strategies which may act as either complementary or an alternative treatment to the standard therapy protocols of HCC. This review focuses on potential cellular and molecular targets, as well as the role of virotherapy and combinational therapy in the treatment of HCC.

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Acknowledgements

This work was supported by research Grants R01 HL116042, R01 HL112597, and R01 HL120659 to DK Agrawal from the National Heart, Lung and Blood Institute, National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, 68178, USA

    Vikrant Rai, Joe Abdo, Swati Agrawal & Devendra K. Agrawal

  2. Department of Pathology, Creighton University School of Medicine, Omaha, NE, 68178, USA

    Abdullah N. Alsuwaidan & Poonam Sharma

  3. Department of Clinical & Translational Science, The Peekie Nash Carpenter Endowed Chair in Medicine, CRISS II Room 510, 2500 California Plaza, Omaha, NE, 68178, USA

    Devendra K. Agrawal

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  1. Vikrant Rai
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Correspondence to Devendra K. Agrawal.

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The authors have no other relevant affiliations or financial involvement with any organization or entity with the financial interest or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

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Rai, V., Abdo, J., Alsuwaidan, A.N. et al. Cellular and molecular targets for the immunotherapy of hepatocellular carcinoma. Mol Cell Biochem 437, 13–36 (2018). https://doi.org/10.1007/s11010-017-3092-z

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