Role of innate immunity in the development of hepatocellular carcinoma

Aravalli, Rajagopal N.

doi:10.3748/wjg.v19.i43.7500

Cited by 48 publications

(44 citation statements)

References 167 publications

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“…In previous studies, chronic infection or excessive responses to commensal organisms has been linked to the development of neoplasia in several gastrointestinal or even nongastrointestinal organs (34–36). The mechanism proposed to explain these associations involved activation of Toll-like receptor (TLR) signaling and its subsequent effects on cell survival and activation.…”

Section: Discussionmentioning

confidence: 99%

Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses

et al. 2016

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Chronic infection with the bacterial Helicobacter pylori is a major cause of gastric and duodenal ulcer disease, gastric mucosal atrophy, and cancer. H. pylori–induced expression of the intestinal epithelial–specific transcription factor caudal-related homeobox 2 (Cdx2) contributes to intestinal metaplasia, a precursor event to gastric cancer. Given a role for the bacterial pattern recognition molecule nucleotide-binding oligomerization domain 1 (NOD1) in the innate immune response to bacterial infection, we investigated mechanisms used by NOD1 to regulate H. pylori infection and its propensity towards the development of intestinal metaplasia. We found that Cdx2 was induced by H. pylori infection in both normal and neoplastic gastric epithelial cells in a manner that was inversely related to NOD1 signaling. Mechanistic investigations revealed that Cdx2 induction relied upon activation of NF-κB but was suppressed by NOD1-mediated activation of TRAF3, a negative regulator of NF-κB. In vivo, prolonged infection of NOD1-deficient mice with H. pylori led to increased Cdx2 expression and intestinal metaplasia. Furthermore, gastric epithelial cells from these mice exhibited increased nuclear expression of the NF-κB p65 subunit and decreased expression of TRAF3. Overall, our findings illuminated a role for NOD1 signaling in attenuating H. pylori–induced Cdx2 expression in gastric epithelial cells, suggesting a rationale to augment NOD1 signaling in H. pylori–infected patients to limit their risks of accumulating precancerous gastric lesions.

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Section: Discussionmentioning

confidence: 99%

Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses

et al. 2016

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“…Factors promoting tumor antigen tolerance, such as decreased recognition of malignant cells, suppression of immunity, and chronic inflammation (either mediated by virus [8] or immune dysregulation), all lead to carcino genesis [9] . Recent studies have provided evidence that a dysregulated immune system, including changes in the number or function of immune cells, cytokine levels, and expression of inhibitory receptors or their ligands significantly contribute to the development of HCC [10,11] . Alterations in the function or expression of immune components shift the immune response towards tumor tolerance, resulting in its progression.…”

Section: Introductionmentioning

confidence: 99%

Immunology of hepatocellular carcinoma

Sachdeva

Chawla

Arora

2015

WJH

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Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system (including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells (e.g. , dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.

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“…In particular, the activation of Toll-like receptor signaling results in the generation of immune responses that often result in the production of pro-inflammatory cytokines and chemokines, and could cause acute inflammation in the liver [34].…”

Section: Discussionmentioning

confidence: 99%

Study of toll-like receptor 7 expression and interferon α in Egyptian patients with chronic hepatitis C Infection and Hepatocellular Carcinoma

Abdel-Raouf

Ahmed

Zaki

et al. 2014

Egyptian Journal of Medical Human Genetics

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Background: Hepatitis C virus is considered to be one of the most important devastating causes of chronic hepatitis, cirrhosis, and hepatic cellular carcinoma. Toll-like receptor 7 (TLR7) is a pathogen-recognition receptor that is expressed on innate immune cells. It recognizes viral RNA which induces its activation with a subsequent increase in IFN-a transcription. It has been postulated that HCV may cause down regulation of these receptors as one of immune evading mechanisms that participate in viral persistence.The aim of the work: Was to investigate the expression of TLR7 in peripheral blood of patients with chronic HCV infections and patients with HCC, comparing it with normal individuals, and correlating it with both serum levels of IFN-a and viral load.Results: The results of this study showed a significant decrease in TLR7 expression in patients with chronic HCV and no detection at all in patients with HCC, in addition a significant negative correlation was observed between levels of TLR7expression and interferon a when compared to viral load.Conclusion: Down regulation of TLR7 expression in HCV and HCC patients may contribute to the decrease of IFN-a and increase in viral load. These results raise the possibility that by targeting TLR7 with high affinity pharmacological stimulants may be able to control HCV infection by induction of IFN-a and direct activation of antiviral mechanisms in hepatocytes. Additionally, they provide insight about the potential use of TLR7 as a new set of molecular markers for prognosis and outcomes of chronic HCV infection and HCC.Ó 2014 Production and hosting by Elsevier B.V. on behalf of Ain Shams University.

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Role of innate immunity in the development of hepatocellular carcinoma

Cited by 48 publications

References 167 publications

Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses

Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses

Immunology of hepatocellular carcinoma

Study of toll-like receptor 7 expression and interferon α in Egyptian patients with chronic hepatitis C Infection and Hepatocellular Carcinoma

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