Inflammatory education of liver resident cells and its long-term effect on liver metastasis formation

Project Details

Description

Metastasis is the major cause of death in cancer patients and progress in the prevention and treatment of metastatic disease is lagging behind. The liver is often the target organ of metastasis in multiple cancer types, encompassing gastrointestinal cancers, but also melanoma, breast and renal cancer. The level of liver involvement is often a decisive factor in the survival of these patients, given
its vital functions and the frequently inoperable state of the affected liver. Disseminated cancer cells can be transported via the portal vein or the hepatic artery to end up in the hepatic sinusoids, the luminal side of which is home to the liver-resident macrophages or Kupffer Cells (KCs). These are the prime cells to detect and destroy incoming cancer cells, but these cells are also educated by a distant tumor to regulate liver metastasis formation.
In this proposal, we will investigate to what extent an inflammatory insult to the liver provokes a long-term epigenomic education of liver-resident cells, with an emphasis on KCs. We will expose mice to two main causes of liver inflammation: drug-induced liver inflammation and infectious liver inflammation, and we will evaluate whether this inflammatory education results in an altered
responsiveness of KCs to cancer cells and liver metastasis formation. If so, we will assess the epigenomic changes that occurred in the liver and in trained KCs and we will test KC-derived molecules for their impact on liver metastasis.
AcronymFWOTM1265
StatusActive
Effective start/end date1/11/2431/10/28

Keywords

  • liver metastasis
  • Kupffer Cell
  • trained immunity

Flemish discipline codes in use since 2023

  • Cancer biology
  • Innate immunity
  • Hepatology