NK-cell target immunotherapy for Hepatocellular carcinoma (HCC)

Natural killer (NK) cell immunotherapies have recently been gaining traction for treatment of both hematological and solid tumors due to their innate anti-tumor characteristics. NK cell activity is characterized by a balance of activating and inhibitory receptor interactions rather than antigen recognition, rendering this innate lymphoid cell a promising therapeutic target that does not rely on prior sensitization. Immunotherapies focused on targeting NK cell activity in the form of adoptive transfer, immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) NK cells have shown some success in combating immunosuppressive effects seen during cancer. Significant suppression of NK cells has been identified in the most common type of liver cancer, hepatocellular carcinoma (HCC). NK cells play a pivotal role in the liver by early recognition and lysis of virally infected and cancerous cells introduced through portal circulation and unsurprisingly, dysfunction of this immune cell subset due to the hypoxic HCC microenvironment has been implicated as strongly correlated with poorer prognosis and decreased survival of HCC patients. Research investigating the effects of NK cell suppression has indicated that targeting NK cell suppressive interactions mediates increased lysis of HCC cells. Our research has shown the upregulation of immunosuppressive NK cell ligands on HCC cells that could potentially lead to immune escape mechanisms in HCC cells. Research further elucidating receptor-ligand interactions involved in suppression of NK cell activity during HCC could provide insight into potential therapeutic targets for patients who are untreatable with conventional therapies.