Figure 2.

Aberrant complement activation: a driver for disease progression in hepatocellular carcinoma. A schematic of the liver microenvironment depicting the transition of a healthy immunologically quiescent intrahepatic microenvironment to dysregulated immune status following activation cues to the complement system. In a healthy liver, immune and epithelial cells function in synergy to preserve normal architecture of bile ducts, quiescence of complement molecules, and homeostasis of immune cells. Complement activating disease-triggering signals orchestrate the evolution of dysregulated complement molecules (increased C3, C5, etc) and altered complement regulatory factors (CFH, etc). These acute and/or chronic sustenance of dysregulated complement molecules and their complex interaction with the immune and epithelial cell compartments drive the progression of hepatocellular carcinoma (HCC). Loss of complement regulatory factors and divergent activation of the complement system leads to abnormal hepatocyte architecture, deranged cellular and effector functions, and reactive bile duct profiles. Cumulatively, these events lead to epithelial to mesenchymal transition (EMT) and tumor angiogenesis which worsen the disease, resulting in poor clinical outcomes and death.