The Immune System is the Final Answer for against HCC

Abstract

T-cells play a critical role in immune responses against cancer. Cytotoxic T-lymphocytes (CTL) are one class of effector T-cells that secrete cytokines and can specifically lyse target cells. However, on prolonged antigenic stimulation, T-cells may lose their effector functions even in the presence of antigens that hey target. Such an 'exhaustion' state renders T-cells incapable of clearing pathogens or eliminating neoplastic cells. Immune checkpoints provide a regulatory feedback mechanism to limit the effector phase of T cell differentiation. They play key parts in tolerance to self antigens, and provide the basis for finetuning of the T-cell response. PD1 is a transmembrane receptor. It binds to two ligands, programmed cell death protein 1 ligand 1 (PDL1), and PDL2, both of which are transmembrane proteins as well. PDL1 expression is a major mechanism by which tumor cells can evade immune attack. Immune checkpoint modulators have recently emerged and offer encouraging results in cancer treatment. Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody and it has been tested clinically in a series of CheckMate studies. Interaction of hepatocellular carcinoma (HCC) with the immune system plays a major role in its progression. Inadequate co-stimulation, failure of antigen recognition and processing, along with suppression of effector cells are proposed mechanisms that result in weakened immune response in HCC patients. Notably, PD-L1 is over-activated in HCC, and its receptor is found to inhibit T-cell activation. In the presentation, we will discuss about the emerging data about the use of anti-PD 1 and its combination in advanced HCC population.