Locoregional immuno(bio)therapy for liver metastases

Despite advances in locoregional chemotherapy, treatment of metastatic liver tumors remains a challenge. Since the liver is the largest organ of the reticuloendothelial system, locoregional immunotherapy would be a reasonable approach for the management of hepatic metastases. Indeed, various immunological approaches have been explored. Regional infusion of cytokines such as interleukin 2 (IL-2) or tumor necrosis factor-alpha (TNF-alpha) through the hepatic artery or the portal vein has been combined with chemotherapy and demonstrated to be better than chemotherapy alone. Locoregional adaptive immunotherapy (AIT) using lymphokine-activated killer (LAK) cells or tumor-infiltrating lymphocytes (TIL) has also been tried with rather disappointing responses. Addition of immunostimulants such as OK-432 to AIT increased clinical responses. Recently, several new approaches have emerged to improve the outcome of locoregional immunotherapy. Embolization of melanoma metastatic to the liver with a granulocyte-macrophage colony-stimulating factor (GM-CSF)/ethiodized oil emulsion resulted in control of liver metastases, as well as development of significant immune responses in remote extrahepatic metastases. A gene therapy designed to introduce foreign major histocompatibility complex (MHC) molecules in colorectal metastases has proven to be a safe and feasible approach. Larger scale clinical trials are mandatory to define the role of locoregional immunotherapy for metastatic tumors in the liver.