Single cell profiling reveals window for immunotherapy in liver cancers

Primary liver cancer has the second highest mortality rate with more than 700,000 deaths. Hepatocellular carcinoma (HCC), the most prevalent tumor type in the liver, arises predominantly from hepatocytes and is often related to known etiologies such as chronic hepatitis B or C virus, obesity, diabetes mellitus, metabolic liver diseases and life style factors (for example, alcohol). The injury to the liver parenchyma, these risk factors induce, causes an inflammatory milieu, which initiates a chain of accumulative events by producing reactive oxygen species (ROS), inflammatory cytokine and chemokine release as well as chromosomal instability. In this milieu, progressions of cellular death (necrosis) and regeneration result in liver fibrosis. In the background of the damaged liver, molecular alterations accrue contributing to the initiation of HCC. This multi-step progression and a detailed understanding of the genetic and epigenetic events that define HCC development remain challenging. The severity of this malignancy is further complicated since it commonly is associated with underlying cirrhosis, which clinically is problematic for the advancement of therapeutic options.