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Semin Liver Dis 2019; 39(01): 026-042
DOI: 10.1055/s-0038-1676806
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inflammation and Liver Cancer: Molecular Mechanisms and Therapeutic Targets

Yoon Mee Yang
1   Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
,
So Yeon Kim
1   Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
,
Ekihiro Seki
1   Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
› Author Affiliations Funding This work was supported in part by the National Institutes of Health (NIH) (R01DK085252, R21AA025841, T32HL134637), the American Liver Foundation (ALF; Irwin M. Arias, MD, Postdoctoral Research Fellowship), and Cedars-Sinai Medical Center (Winnick Research Award, Samuel Oschin Comprehensive Cancer Institute-Center for Integrated Research in Cancer and Lifestyle Award).
Further Information

Publication History

Publication Date:
17 January 2019 (online)

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Abstract

Hepatocellular carcinoma (HCC) is associated with chronic inflammation and fibrosis arising from different etiologies, including hepatitis B and C and alcoholic and nonalcoholic fatty liver diseases. The inflammatory cytokines tumor necrosis factor-α and interleukin-6 and their downstream targets nuclear factor kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and signal transducer and activator of transcription 3 drive inflammation-associated HCC. Further, while adaptive immunity promotes immune surveillance to eradicate early HCC, adaptive immune cells, such as CD8+ T cells, Th17 cells, and B cells, can also stimulate HCC development. Thus, the role of the hepatic immune system in HCC development is a highly complex topic. This review highlights the role of cytokine signals, NF-κB, JNK, innate and adaptive immunity, and hepatic stellate cells in HCC and discusses whether these pathways could be therapeutic targets. The authors will also discuss cholangiocarcinoma and liver metastasis because biliary inflammation and tumor-associated stroma are essential for cholangiocarcinoma development and because primary tumor-derived inflammatory mediators promote the formation of a “premetastasis niche” in the liver.

Keywords

NF-κB - apoptosis - hepatic stellate cells - ER stress - immune checkpoint inhibitor
 

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