Dual regulatory role of invariant natural killer T cells in the development and progression of hepatocellular carcinoma

Our project aims to examine the role of Invariant Natural Killer T cells (iNKT) in Hepatocellular Carcinoma (HCC) which is not known. HCC is a leading cause of death and accounts for ~80% of cases of liver cancer worldwide. Because there are no biomarkers that allow the early diagnosis, HCC is diagnosed at late stages when the tumor is developed enough and is resistant to chemotherapy. The liver is characterized by an immunosuppressive environment and due to this environment, liver is prone to HCC development. Once HCC is developed, the function of immune cells that fight the tumor such as dendritic cells, natural killer cells, helper and cytotoxic T cells is suppressed while the function of regulatory T cells and myeloid- derived suppressor cells is enhanced. However, the role of Natural Killer T cells (NKT) is not known. NKT cells is a population of the immune system which is largely enriched in the liver, which recognize lipid antigens by CD1d molecule and can rapidly produce large amounts of various cytokines to enhance the function of other immune populations. Here, we investgated the role of NKT cell in chemical-induced HCC that recapitulates the development of human HCC usiing genetic models that lack or overproduce NKT cells. Hepatic Invariant Natural Killer T (iNKT) cells, identifed as CD1D-PBS57-tetramer+Tcrb+ cells, were isolated through FACS sorting from two healthy WT mice (controls) and three WT mice with DEN-induced hepatocellular carcinoma