Toll-like receptors in hepatocellular carcinoma: potential novel targets for pharmacological intervention

ABSTRACT

Introduction: Toll-like receptors (TLRs) are expressed by a wide variety of cell types including immune cells. They play a crucial role in the inflammatory and host defense response against microorganisms, and triggering TLRs can mediate the activation of innate immunity. Furthermore, research suggests that various TLRs may function differently on different tumor cells. The change in TLR activity may elicit an anti-tumor activity in hepatocellular carcinoma (HCC) cells and may serve as a novel therapeutic target for HCC therapy.

Areas covered: This review discusses the role of the TLR family in HCC and the underlying signaling pathway of TLRs as a form of pattern recognition receptor in mediating inflammation and HCC immunity responses. Agonists and antagonists of TLRs, which render TLRs as potential therapeutic targets, activate downstream molecules, subsequently causing HCC cell survival. The proliferation or protection against the development of HCC is also described.

Expert opinion: A series of studies have highlighted a crucial role of TLRs in HCC and consider TLR signaling pathways as potential therapeutic targets for HCC. However, the conclusions of these studies are in part paradoxical and controversial. Thus, it is necessary to extend further research to help determine the signaling pathways involved.

KEYWORDS:

• Toll-like receptors
• hepatocellular carcinoma
• mechanism
• tumorigenesis
• targets

Article highlights

• The distribution of the TLR family on human liver.

• TLRs can be promising potential therapeutic targets for HCC.

• The signaling pathway of TLRs in HCC.

• A relationship between TLRs expression and the features of cancer stem cells (CSCs).

• The role of agonists and antagonists of TLRs in HCC.

This box summarizes key points contained in the article.

Declaration of interest

The authors were supported by grants from National Natural Science Foundation of China (81500665, 81300311), Health Bureau of Zhejiang Province (2010KYB070), Research Foundation of Education Bureau of Zhejiang Province (Y201009942), the Opening Project of Zhejiang Provincial Top Key Discipline of Pharmaceutical Sciences and Project of New Century 551 Talent Nurturing in Wenzhou. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.