Role of innate immunity in the development of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. It is caused by a variety of risk factors, most common ones being infection with hepatitis viruses, alcohol, and obesity. HCC often develops in the background of underlying cirrhosis, and even though a number of interventional treatment methods are currently in use, recurrence is fairly common among patients who have had a resection. Therefore, whole liver transplantation remains the most practical treatment option for HCC. Due to the growing incidence of HCC, intense research efforts are being made to understand cellular and molecular mechanisms of the disease so that novel therapeutic strategies can be developed to combat liver cancer. In recent years, it has become clear that innate immunity plays a critical role in the development of a number of liver diseases, including HCC. In particular, the activation of Toll-like receptor signaling results in the generation of immune responses that often results in the production of pro-inflammatory cytokines and chemokines, and could cause acute inflammation in the liver. In this review, the current knowledge on the role of innate immune responses in the development and progression of HCC is examined, and emerging therapeutic strategies based on molecular mechanisms of HCC are discussed.

Keywords: Hepatocellular carcinoma; Innate immunity; Toll-like receptor; Liver cancer; Inflammation

Core tip: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Growing incidence of HCC has generated immense interest to understand the mechanisms of disease at the physiological, cellular and molecular levels with the hope of developing novel therapeutics for the treatment of HCC. In the past few years, it has become clear that innate immunity plays a critical role in the development and progression of HCC. In this review, these new developments and possibilities of developing novel therapeutic options based on this newly gained knowledge are discussed.