Characterizing and combating the immune modulatory and epithelial-to-mesenchymal plasticity properties of hepatocellular carcinoma-derived cancer stem cells

Background: Hepatocellular carcinoma (HCC) is the fastest increasing cause of cancer mortality in Australia despite the development of various therapeutic strategies. The development of an effective immunotherapy for HCC has proven difficult, with the induction of anticancer-directed immune responses seldom resulting in complete tumor eradication. Understanding the mechanisms by which cancer cells are able to escape host immune responses is critical for the development of successful immunotherapeutic treatments. Cancer stem cells (CSCs) represent a specialized population of transformed cells distinct from the majority of “differentiated” tumor cells. These cells are responsible for tumor initiation, organization and maintenance and play a major role in the resistance to radiation and chemotherapy. Recently, epithelial-to-mesenchymal plasticity (EMP) that enables tumor metastasis has emerged as an important regulator of CSC immune modulation. Despite the importance of CSCs, very little is known about the sensitivity of these cells to immune surveillance and immune killing in HCC.