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
