Affordable Access

Access to the full text

Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer

Authors
  • Lurje, Isabella
  • Hammerich, Linda
  • Tacke, Frank
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Oct 06, 2020
Volume
21
Issue
19
Identifiers
DOI: 10.3390/ijms21197378
PMID: 33036244
PMCID: PMC7583774
Source
PubMed Central
Keywords
License
Green

Abstract

Liver fibrosis is a chronic, highly prevalent disease that may progress to cirrhosis and substantially increases the risk for development of hepatocellular carcinoma (HCC). Fibrotic livers are characterized by an inflammatory microenvironment that is composed of various immunologically active cells, including liver-resident populations (e.g., Kupffer cells, hepatic stellate cells and sinusoidal endothelium) and infiltrating leukocytes (e.g., monocytes, monocyte-derived macrophages, neutrophils and lymphocytes). While inflammatory injury drives both fibrogenesis and carcinogenesis, the tolerogenic microenvironment of the liver conveys immunosuppressive effects that encourage tumor growth. An insufficient crosstalk between dendritic cells (DCs), the professional antigen presenting cells, and T cells, the efficient anti-tumor effector cells, is one of the main mechanisms of HCC tumor tolerance. The meticulous analysis of patient samples and mouse models of fibrosis-HCC provided in-depth insights into molecular mechanisms of immune interactions in liver cancer. The therapeutic modulation of this multifaceted immunological response, e.g., by inhibiting immune checkpoint molecules, in situ vaccination, oncolytic viruses or combinations thereof, is a rapidly evolving field that holds the potential to improve the outcome of patients with HCC. This review aims to highlight the current understanding of DC–T cell interactions in fibrogenesis and hepatocarcinogenesis and to illustrate the potentials and pitfalls of therapeutic clinical translation.

Report this publication

Statistics

Seen <100 times