Immune suppressor mechanisms in HCC

Abstract

The liver has been recognized as a tolerogenic organ. This is based on clinical experience in the transplant setting, where immunosuppression is dosed relatively low or can even be discontinued in selected patients over time. Furthermore, the liver is showered with many antigens from the gastrointestinal tract delivered through the portal vein without causing active immune responses. In contrary, tumor-specific immune responses against tumors arising in the liver have been observed. Tumors have developed multiple molecular and cellular mechanisms to escape from anti-tumor immunity. An increase in the frequency of myeloid derived suppressor and regulatory T cells, two cell types with potent immune suppressor function has been described in patients with HCC and shown to correlate with worse outcome. Kupffer cells represent another immune cell with immunosuppressive function and different cytokines as well as cell surface molecules such as PD1/PD-L1 have been described. A better understanding of the immunosuppressive microenvironment in the liver will help better understand the development and growth of HCC and provide opportunities to specifically target mechanism leading to enhanced anti-tumor immunity and better outcome.