NAFLD Indirectly Impairs Antigen Specific CD8 + T Cell Immunity Against Liver Cancer in Mice

Non-alcoholic fatty liver disease (NAFLD) has become an important etiology leading to liver cancer. NAFLD alters adaptive T cell immunity and has a profound influence on liver cancer development. However, it is unclear how NAFLD affects tumor antigen specific T cell responses. In this study, we generated a doxycycline inducible MHC-I and II antigen expressing HCC cell line which allowed us investigate tumor antigen specific T cell response in two NAFLD mouse models. The system proved to be an effective and efficient way to study tumor antigen specific T cells. Using this model, it was found that NAFLD impairs antigen specific CD8+ T cell immunity against liver cancer. The effect was not due to reduced generation or intrinsic functional changes of tumor antigen specific CD8+ T cells but caused by accumulated macrophages in liver environment. The findings suggest that targeting macrophages in NAFLD driven HCC may improve therapeutic outcomes.