Hepatitis C virus drives the pathogenesis of hepatocellular carcinoma: from immune evasion to carcinogenesis

Abstract

Persistent hepatitis C virus (HCV) infection is associated with high incidence of hepatocellular carcinoma (HCC), the most common primary malignancy of the liver with over half a million new cases diagnosed annually worldwide. The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed transcription factor and its activation by environmental chemicals and by its endogenous ligand kynurenine (Kyn) has been implicated in a variety of tumour-promoting processes such as transformation, tumorigenesis and in immunosuppression that enables tumour survival and growth. Kyn is generated constitutively by human tumour cells via tryptophan (Trp)-2,3-dioxygenase (TDO), a Trp-degrading enzyme expressed in liver, brain and cancer cells. Notably, it has been shown that TDO-derived Kyn suppresses anti-tumour immune responses, thus promoting tumour-cell survival through activation of the AhR pathway. In the context of HCV infection-associated HCC, it was shown that AhR signalling is increased in HCV-infected hepatocytes, and that modifications in the expression of AhR pathway-specific genes are associated with the progression of HCV infection into HCC. Based on these observations, we present and discuss here the hypothesis that HCV infection promotes HCC by modulation of the TDO–Kyn–AhR pathway, resulting in tumorigenesis as well as in suppression of both anti-HCV and anti-tumour immune responses.

Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives

“…In Asia, infection with hepatitis B virus is the more common cause of HCC, while in the United States, hepatitis C virus (HCV) is a more common etiologic agent. HCV may also possess a higher capacity to evade the immune system ( 128 ). As of today, we still do not have an effective vaccine against HCV, and we would hypothesize that liver cancers (mostly HCC) resulting from chronic HCV infection may be generally less immunogenic than those tumors caused by HBV infection.…”

Hepatic Hippo signaling inhibits protumoural microenvironment to suppress hepatocellular carcinoma

“…Hepatocellular carcinoma (HCC), a primary malignancy of the liver, is a major health problem, being the fifth most common cancer and second leading cause of cancer deaths in the world [2, 3]. In most cases, human HCC is driven by chronic liver inflammation caused by activation of many types of inflammatory cells due to chronic viral hepatitis, metabolic liver diseases and alcohol abuse [4]. Among them, macrophages derived from circulating monocytic precursors are key components involved in the initiation and maintenance of inflammation, fibrosis and cancer progression and they are normally the most abundant immune cells in the tumor microenvironment [5].…”

Interleukin-28B Polymorphism is a Pharmacogenetic Predictor during Sofosbuvir Plus Pegylated Interferon and Ribavirin Therapy for Chronic Hepatitis C Egyptian Patients

“…HCV can lead to chronic hepatitis disease in millions of people and are the most common cause of liver cirrhosis and hepatocellular carcinoma [11]. Seven HCV genotypes and sixty seven subtypes have been identified [12].…”