Sorting Out Pandora’s Box: Discerning the Dynamic Roles of Liver Microenvironment in Oncolytic Virus Therapy for Hepatocellular Carcinoma

摘要: Oncolytic viral therapies have recently found their way into clinical application for hepatocellular carcinoma (HCC), a disease with limited treatment options and poor prognosis. Adding to the many intrinsic challenges of in vivo oncolytic therapy, is complex microenvironment liver, which imposes unique limitations successful delivery propagation virus. The normal liver milieu characterized by an intricate network hepatocytes non-parenchymal cells including Kupffer cells, stellate sinusoidal endothelial can secrete anti-viral cytokines, provide platform non-specific uptake, form barrier efficient spread. In addition, natural killer are greatly enriched contributing innate defense against viruses. situation further complicated when HCC arises setting underlying hepatitis virus infection and/or hepatic cirrhosis, occurs more than 90% cases. These conditions pose inhibitory effects on (OV) therapy due presence chronic inflammation, constitutive cytokine expression, altered blood flow, extracellular matrix deposition. OVs modulate microenvironment, resulting interplay between host. immune system undoubtedly plays substantial role outcome OV both as inhibitor replication, potent mechanism virus-mediated tumor cell killing. This review will discuss particular HCC, well some potential strategies modulating synergizing improve therapeutic outcome.